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Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health. [ABSTRACT FROM AUTHOR]

Background: The typical onset of schizophrenia coincides with the maturational peak in cognition; however, for a significant proportion of patients the onset is before age 18 and after age 30 years. While cognitive deficits are considered core features of schizophrenia, few studies have directly examined the impact of age of illness onset on cognition. Methods: The aim of the study was to examine if the effects of age on cognition differ between healthy controls (HCs) and patients with schizophrenia at illness onset. We examined 156 first-episode antipsychotic-naïve patients across a wide age span (12–43 years), and 161 age- and sex-matched HCs. Diagnoses were made according to ICD-10 criteria. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), and IQ was estimated using subtests from the Wechsler adult- or child-intelligence scales. Multivariate analysis of covariance (MANCOVA) was used to examine linear and quadratic effects of age on cognitive scores and interactions by group, including sex and parental socioeconomic status as covariates. Results: There was a significant overall effect of age on BACS and IQ (p < 0.001). Significant group-by-age interactions for verbal memory (for age-squared, p = 0.009), and digit sequencing (for age, p = 0.01; age-squared, p < 0.001), indicated differential age-related trajectories between patients and HCs. Conclusions: Cognitive functions showing protracted maturation into adulthood, such as verbal memory and verbal working memory, may be particularly impaired in both early- and late-schizophrenia onset. Our findings indicate a potential interaction between the timing of neurodevelopmental maturation and a possible premature age effect in late-onset schizophrenia. [ABSTRACT FROM AUTHOR]

Highlights • We investigated the relationship between changes in the striatal volume and symptoms of ARMS. • Right putamen volume reduction was observed in ARMS who did not develop psychosis (ARMS-N). • Changes in sub-threshold symptoms and the volume of the accumbens were correlated in ARMS-N. • No correlation for negative symptoms. Abstract Recent studies have revealed that several psychotic symptom changes observed in the 'at risk mental state' (ARMS) are associated with changes in the striatum. We investigated if structural changes in the striatum are associated with recovery of sub-threshold psychotic symptoms in subjects with an ARMS who did not develop psychosis (ARMS-N). Sixteen healthy controls and 42 subjects with an ARMS participated in this study. Striatal volumes (caudate, putamen, and nucleus accumbens) were analyzed using MRI. The sub-threshold psychotic symptoms of the subjects with an ARMS were measured using the SOPS. Imaging and symptoms were reevaluated after 52 weeks. Significant right putamen volume reduction was observed at the follow-up in ARMS-N subjects. Improvement in sub-threshold positive symptoms significantly correlated with an increase in volume in the right accumbens at follow up. No relationship was found for negative symptoms. From these findings, the association between improvement in sub-threshold positive symptoms and an increase in the volume of the right accumbens may suggest that changes in the accumbens, which is a major site for dopamine innervation, are associated with symptom recovery. These findings may point to neurobiological resilience that may be associated with lower transition to psychosis. [ABSTRACT FROM AUTHOR]

Previous studies have revealed that changes in sub-threshold psychotic symptoms observed in individuals with an ‘at risk mental state’ (ARMS) are associated with biological changes in the corpus callosum (CC). To elucidate the biological background for resilience against transition to psychosis, we investigated the relationship between CC structural changes and recovery of sub-threshold psychotic symptom in subjects with ARMS who did not develop psychosis (ARMS-N). Sixteen healthy controls and 42 ARMS (37 ARMS-N) subjects participated this study. The volumes of five sub-regions of the CC were analyzed using MRI. The sub-threshold psychotic symptoms of the ARMS were measured using the Scale of Prodromal Symptoms (SOPS). Imaging and symptoms were re-administered in the ARMS group 52 weeks later. Significant baseline volume differences in the mid-posterior CC, central CC and mid-anterior CC were found between the controls and the ARMS-N subjects. These findings suggest that biological abnormalities are present in a so-called “false-positive” group of individuals. For the ARMS-N subjects, improvement in negative symptoms significantly correlated with an increase in the volume of the central CC at follow-up. This finding may suggest that a neurobiological ‘resilience’ is associated with symptom recovery. [ABSTRACT FROM AUTHOR]

A series of parallel, integrated circuits link distinct regions of prefrontal cortex with specific nuclei of the striatum and thalamus. Dysfunction of these fronto-striato-thalamic systems is thought to play a major role in the pathogenesis of psychosis. In this review, we examine evidence from human and animal investigations that dysfunction of a specific dorsal fronto-striato-thalamic circuit, linking the dorsolateral prefrontal cortex, dorsal (associative) striatum, and mediodorsal nucleus of the thalamus, is apparent across different stages of psychosis, including prior to the onset of a first episode, suggesting that it represents a candidate risk biomarker. We consider how abnormalities at distinct points in the circuit may give rise to the pattern of findings seen in patient populations, and how these changes relate to disruptions in dopamine, glutamate and GABA signaling. [ABSTRACT FROM AUTHOR]

Objective: Cognitive dysfunction is a common characteristic of both schizophrenia and bipolar disorder (BP). While these deficits are more severe in schizophrenia, there is a significant overlap between conditions. However, it was hypothesized that social cognitive deficits might be more specific to schizophrenia.Methods: We conducted a meta-analysis of studies comparing facial emotion recognition and theory of mind (ToM) abilities in schizophrenia and BP. 26 studies comparing 1301 patients with schizophrenia and 1075 with BP were included.Results: Schizophrenia patients significantly underperformed compared with BP patients in both facial emotion recognition (d=0.39) and ToM (d=0.57). Neurocognitive deficits significantly contributed to schizophrenia-BP group differences for ToM. However, between-group differences for social cognition were not statistically more severe than neurocognition.Conclusion: Social cognitive impairment is more severe in schizophrenia in comparison to BP. However, between-group differences are modest and are comparable to other neurocognitive differences between schizophrenia and BP. There is significant overlap in social cognitive performance deficits observed in both schizophrenia and BP. [ABSTRACT FROM AUTHOR]

Background Evidence supports disruption in white matter (WM) connectivity in established schizophrenia, however, it is unclear when these abnormalities occur during the course of illness and if they are progressive. Here we investigated whether WM abnormalities predate illness onset by examining a group of individuals with an ‘at risk mental state’ (ARMS) and assess whether there is evidence of progressive change. We hypothesized that WM abnormalities are associated with symptom change. Methods Sixteen healthy controls and 41 ARMS subjects at baseline underwent Diffusion Tensor Imaging (DTI). Sub-threshold positive symptoms were measured using the Scale of Prodromal Symptoms (SOPS). Imaging and symptoms were re-administered in the ARMS group after one year (52 weeks). Fractional anisotropy (FA) value differences between ARMS and control groups at baseline were localized using the method of Tract-Based Spatial Statistics (TBSS). Results At baseline, FA was significantly reduced in a sub-region of the corpus callosum (CC) in the ARMS group as a whole compared to controls. This reduction was also found in the 34 individuals who did not transition (ARMS-N) during the one-year follow-up. However, the ARMS-N group showed a significant improvement in sub-threshold positive symptoms at follow-up, which was correlated with an increase in FA in the same CC region (r = − 0.664, p < 0.001). Discussion There was a significant FA reduction in the CC in individuals at high risk for psychosis regardless of transition status at one year. This suggests that WM abnormalities in the CC may represent a biological vulnerability to psychosis. Improvement in sub-threshold positive symptoms was associated with improvement in measures of WM integrity in the CC. This may suggest that neurobiological ‘resilience’ is associated with improved outcomes, although this notion requires future study. [ABSTRACT FROM AUTHOR]

Highlights: [•] Impaired human cognitive abilities are reflected by loss of olfactory abilities. [•] We examined olfactory abilities in three neurogenerative disorders. [•] Parkinson's disease, Type 1 myotonic dystrophy and Alzheimer's disease were tested. [•] All patients exhibited decreased or impaired odor-recognition compared with age-matched controls. [Copyright &y& Elsevier]

Abstract: Theory of mind (ToM) deficit is a well-established feature of schizophrenia and has been suggested as a vulnerability marker of this disorder. However, as most of this evidence is based on studies in chronic patients, it is less clear whether ToM is impaired prior to or following the onset of a first-episode and whether it is evident in unaffected relatives of patients. In this meta-analysis, ToM performance of 3005 individuals with first-episode psychosis (FEP), individuals at ultra-high risk for psychosis (UHR) and unaffected relatives were compared with 1351 healthy controls. ToM was substantially impaired in first-episode psychosis (Cohen d =1.0) and this deficit was comparable to findings in chronic patients. ToM was also impaired in unaffected relatives (d =0.37) and UHR subjects (d =0.45) and performances of these groups were intermediate between FES and healthy controls. Severity of ToM deficits in unaffected relatives and UHR subjects was similar to other cognitive deficits observed in these groups. Longitudinal studies of clinical and genetic high-risk subjects are necessary to investigate the trajectory of development of ToM deficits in schizophrenia. [Copyright &y& Elsevier]

Our objective was to describe the prevalence, comorbidity, and neuropsychological profiles of children with hoarding and learning disabilities. From 61 children with learning disabilities, 16.4% exhibited hoarding as a major clinical issue. Although children with learning disabilities and hoarding displayed greater rates of obsessive-compulsive disorder (30%) as compared to those with learning disabilities without hoarding (5.9%), the majority of patients belonging to the former group did not display obsessive-compulsive disorder diagnosis. When learning disability patients with hoarding were compared to age-, sex-, and IQ-matched learning disability subjects without hoarding, hoarders exhibited a slower learning curve on word list-learning task. In conclusion, salient hoarding behaviors were found to be relatively common in a sample of children with learning disabilities and not necessarily associated with obsessive-compulsive disorder, supporting its nosological independence. It is unclear whether underlying cognitive features may play a major role in the development of hoarding behaviors in children with learning disabilities. [ABSTRACT FROM PUBLISHER]

In this review, we describe neuropsychological and brain imaging findings in the early stages of psychosis and schizophrenia. We focus on recent clinical high-risk studies and consider whether the evidence supports these as ‘endophenotypes’ of a vulnerability to the illness or as ‘biomarkers’ of illness onset and transition. The findings suggest that there are a number of processes at psychosis onset that may represent biomarkers of incipient illness. These neurobiological indices particularly implicate the integrity of frontal and temporal cortices, which may or may not be related to the genetics of psychosis (i.e. potential ‘endophenotypes’). However, these brain regions are dynamically changing during normal maturation, meaning that any putative neurobiological markers identified at the earliest stages of illness may be relatively unstable. We suggest that, while such measures may be readily identified as potential neurobiological markers of established illness, they are inconsistent at (or around) the time of illness onset when assessed cross-sectionally. Instead, identification of more valid risk markers may require longitudinal assessment to ascertain normal or abnormal trajectories of neurodevelopment. Accordingly, we assert that the current conceptualisations of potential biomarkers and/or ‘endophenotypes’ for schizophrenia may need to be reconsidered in the context of normal and abnormal brain maturational processes at the time of onset of psychotic disorders. [ABSTRACT FROM AUTHOR]

Abstract: Patients with established schizophrenia perform poorly on attentional set-shifting tasks, due to a failure of inhibitory control and/or perseverative errors. However, attentional set-shifting is also dependent on working memory capacity, which is additionally impaired in schizophrenia. No studies in first-episode psychosis have specifically examined the contribution of working memory to set-shifting ability in schizophrenia. We investigated 48 first-episode schizophreniform psychosis/schizophrenia (FE) and 40 chronic schizophrenia (CHR) patients, compared to 67 comparable healthy subjects (CTL). All subjects were assessed using the CANTAB ‘attentional set-shifting (IDED)’ and ‘spatial working memory (SWM)’ tasks. Both FE and CHR made significantly greater errors on the SWM task (p ≤0.001). Compared with CTL, CHR was more likely to fail at intra-dimensional (p <0.05) and extra-dimensional (p <0.01) shifting and reversal stages of IDED; CHR required significantly greater trials to reach criterion, which was not explained by deficits in SWM (p <0.001). FE did not differ from CTL on IDED level reached. However, FE required significantly more trials (p =0.001); this was no longer significant after controlling for SWM deficits (p >0.05). Given that the capacity to be flexible and shift attentional set is intact only at the early stages of illness, ‘neurodegenerative’ processes may explain the more severe deficits in chronic schizophrenia. In contrast, deficits in SWM identified at all stages of schizophrenia may reflect incomplete maturation prior to illness onset (‘neurodevelopmental arrest’). Longitudinal studies assessing these cognitive functions from illness onset or in prepsychotic individuals are required. [Copyright &y& Elsevier]

Background: We sought to determine if a representative group of young chronic patients with schizophrenia would demonstrate selective impairments in set shifting processes of the CANTAB Intra-dimensional/extra-dimensional (IDED) task. We predicted that patients would have prominent difficulties with Compound Discrimination (C_D) (stage of the task in which irrelevant stimuli are introduced) and Extra-Dimensional Shifting (EDS) (stage of the task in which a new stimulus dimension must be attended) on the basis of the results of cortical hypodopaminergic states in subhuman primates (for C_D) and effects of dorsolateral prefrontal cortical lesions on set shifting and prior results in schizophrenia (for EDS).Methods: We administered the IDED to 36 patients and 26 healthy controls. Additionally, we administered the Wisconsin Card Sorting Test (WCST), another test of set shifting, and a Continuous Performance Test (CPT) type task of attention to patients with schizophrenia in order to investigate which cognitive components accounted for performance difficulties at different stages of the IDED task.Results: Patients had selective difficulties on C_D and EDS stages of the task. In schizophrenic patients early stages of the task involving the introduction and establishment of attentional set were correlated to CPT performance, while later set shifting stages were correlated with WCST categories attained.Conclusion: We found evidence that patients with schizophrenia were susceptible to introduction of unreinforced irrelevant stimuli at the C_D stage, such that the previously rewarded target stimuli no longer held hegemony as a representation. This type of processing failure may reflect difficulties in stabilizing a representation and is consistent with effects of prefrontal hypodopaminergia in primates. Secondly, "survivors" of this stage experienced marked difficulties on EDS-stage, suggestive of classic prefrontal failures. [ABSTRACT FROM AUTHOR]

Highlights from the article: B Background: b Schizophrenia is a psychiatric disorder with a worldwide prevalence of 1%. The high heritability and reduced fertility among schizophrenia patients have raised an evolutionary paradox: why has negative selection not eliminated schizophrenia associated alleles during the evolution process? Such findings indicated that risk alleles of schizophrenia have been gradually removed from the modern human genome due to negative selection pressure.

To quantitatively explore the level of insight in forensic patients with schizophrenia, and its relationship to symptoms and to a history of violence. In addition, to test the hypothesis that scores in the insight domains of ‘compliance’ and ‘awareness of illness’ are positively correlated with scores on a self-report scale measuring ‘hopelessness’. The study consisted of a cross-sectional survey. Subjects were inpatients and outpatients in the rehabilitation service of the Victorian Institute of Forensic Mental Health. Twenty-eight patients with a diagnosis of schizophrenia and a history of serious offending consented to take part. Twenty-two of these had committed homicide. Measures were obtained for each on the Schedule for Assessment of Insight, the Positive and Negative Syndrome Scale for Schizophrenia and the Beck Hopelessness Scale. The mean insight score for forensic patients was 8.39 (SD 4.88). Insight scores did not differ significantly between those subjects who had a history of violence prior to their index offence and those who did not. Awareness of illness, but not compliance, was positively correlated with level of hopelessness. A higher level of awareness of having a mental illness was thus related to feeling more hopeless about the future. Mean insight scores in patients with schizophrenia with a forensic history do not differ significantly from those in non-forensic populations. Being more aware of being mentally ill may be a risk factor for hopelessness about the future. The limitations of the study are the small sample size, and the fact that it is confined to a relatively clinically stable population. [ABSTRACT FROM AUTHOR]

Objective: The evidence from structural imaging studies supports the notion that schizophrenia arises from an early abnormality in brain development. In this paper we review the timing of structural changes in schizophrenia and argue that schizophrenia is a neuro­developmental disorder with limited progressive brain changes occurring during the evolution and early phase of psychosis. Method: The available cross-sectional and longitudinal studies are reviewed, along with data from our own research. Results: The current literature, including our own data, suggests that structural brain changes are apparent premorbidly, consistent with a neurodevelopmental lesion. These are prominent in frontal and cingulate regions, and appear related to premorbid neuropsychological deficits in executive function. However, there appear to be additional brain changes over the transition to illness and beyond. Conclusions: We propose first, that an early neurodevelopmental insult interacts with either normal or abnormal postpubertal brain maturation to produce further (late neurodevelop­mental) brain structural and functional changes; and second, that the effect of such neurodevelopmental lesions will have different consequences for functions that normally develop early in life, such as memory, compared with functions developing later, such as executive functions. A model is presented suggesting that the structural and functional abnormalities in schizophrenia can be understood as a consequence of the neurodevelopmental stage at which brain changes occur. [ABSTRACT FROM AUTHOR]

Summary: Background: Psychotic disorders, such as schizophrenia, are associated with neuroanatomical abnormalities, but whether these predate the onset of symptoms or develop progressively over the course of illness is unclear. We investigated this issue with MRI to study people with prodromal symptoms who are at ultra high-risk for the development of psychosis. Methods: We did two comparisons, cross-sectional and longitudinal. For the cross-sectional comparison, 75 people with prodromal signs of psychosis were scanned with MRI. After at least 12 months of follow-up, 23 (31%) had developed psychosis and 52 (69%) had not. Baseline MRI data from these two subgroups were compared. For the longitudinal comparison, 21 of the ultra high-risk individuals were scanned again with MRI after at least 12 months. Ten of these had developed psychosis and 11 had not. MRI data from baseline and follow-up were compared within each group of people. Findings: In the cross-sectional comparison, compared with people who did not develop psychosis, those who did develop the disorder had less grey matter in the right medial temporal, lateral temporal, and inferior frontal cortex, and in the cingulate cortex bilaterally. In the longitudinal comparison, when re-scanned, individuals who had developed psychosis showed a reduction in grey matter in the left parahippocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri. In those who had not become psychotic, longitudinal changes were restricted to the cerebellum. Interpretation: Some of the grey-matter abnormalities associated with psychotic disorders predate the onset of frank symptoms, whereas others appear in association with their first expression. [ABSTRACT FROM AUTHOR]

In this paper, we examine a cognitive neuropsychiatric approach to understanding neuropsychiatric disorders by examining recent data in schizophrenia. By understanding and applying this approach, we suggest that the processes underlying the neurobiology of a range of other psychiatric disorders can be understood. Further, an assessment of the brain–behaviour relationships through this emerging discipline provides testable models for further study, using a range of techniques including functional and other imaging techniques. [Copyright &y& Elsevier]

Objective: The thalamus and caudate nucleus are key subcortical structures in the fronto-striato-thalamic pathways that have been implicated in the pathogenesis of schizophrenia. Previous studies have been inconsistent in identifying structural and functional abnormalities in these structures. However, methodologies in these studies have been unreliable and some have not adequately matched patients and controls. Methods: Using algebraically-manipulated double-echo magnetic resonance (MR) images, we developed a reliable method to estimate caudate and thalamic volumes in a group of 13 monozygotic (MZ) twins; eight discordant for schizophrenia and five normal. Initially, volumes were measured on four image types: proton density (PD), T2-weighted, summed (PD + T2) and subtracted (PD-T2) to determine the most reliable method. Results: There was a significant method by region interaction, where caudate volumes measured on PD images were significantly larger than those measured on T2-weighted images, while the opposite was found for thalamic volumes. However, there was no interaction of method by diagnosis. Test-retest reliability was highest for the summed images. Using summed images to measure the volumes of the caudate and thalamus in each twin, we found significantly increased caudate volumes in affected twins compared to their unaffected cotwins, but no significant difference in thalamic volume. Conclusions: Our results in a small sample of MZ twins discordant for schizophrenia do not support the presence of structural abnormalities in the thalamus. The findings in the caudate are consistent with previously reported effects of antipsychotic medication. We also report a reliable method for assessing the volumes of subcortical structures. However, volumetric estimates of brain structures may be dependent on which method is used and the structure being assessed. Such interactions need to be considered in future studies investigating brain structural abnormalities in... [ABSTRACT FROM AUTHOR]

Focuses on the corroboration of findings on anterior cingulate hypoperfusion of schizophrenia and the association with the underlying morphology. Use of positron emission tomography scanning for patients with schizophrenia; Impairment of the anterior cingulate cortex; Stability on the doses of medication.

Examines the correlation between tardive dyskinesia and spatial working memory deficits in schizophrenic patients. Comparison between patients receiving anticholigernics and antipsychotics; Occurrence of neurocognitive deficits in chronic schizophrenics.

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]

Objective: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recent-onset psychosis, the majority of whom were neuroleptic naive. Method: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of whom had not received antipsychotic medication, were compared to 38 age- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. Results: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after controlling for gender, premorbid or current IQ, smoking history, cannabis use, or the effects of medication. Diagnostic subgroups did not differ in olfactory identification ability. The deficits remained stable at 6-month follow-up and were associated with negative symptoms at both time points. No relationship was found between olfactory identification ability and length of either untreated psychosis or illness prodrome. Conclusions: Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms. [ABSTRACT FROM AUTHOR]

Episodic memory ability relies on hippocampal-prefrontal connectivity. However, few studies have examined relationships between memory performance and white matter (WM) microstructure in hippocampal-prefrontal pathways in schizophrenia-spectrum disorder (SSDs). Here, we investigated these relationships in individuals with first-episode psychosis (FEP) and chronic schizophrenia-spectrum disorders (SSDs) using tractography analysis designed to interrogate the microstructure of WM tracts in the hippocampal-prefrontal pathway. Measures of WM microstructure (fractional anisotropy [FA], radial diffusivity [RD], and axial diffusivity [AD]) were obtained for 47 individuals with chronic SSDs, 28 FEP individuals, 52 older healthy controls, and 27 younger healthy controls. Tractography analysis was performed between the hippocampus and three targets involved in hippocampal–prefrontal connectivity (thalamus, amygdala, nucleus accumbens). Measures of WM microstructure were then examined in relation to episodic memory performance separately across each group. Both those with FEP and chronic SSDs demonstrated impaired episodic memory performance. However, abnormal WM microstructure was only observed in individuals with chronic SSDs. Abnormal WM microstructure in the hippocampal-thalamic pathway in the right hemisphere was associated with poorer memory performance in individuals with chronic SSDs. These findings suggest that disruptions in WM microstructure in the hippocampal–prefrontal pathway may contribute to memory impairments in individuals with chronic SSDs but not FEP. [ABSTRACT FROM AUTHOR]

Neurofilament light chain (NfL), a blood biomarker of neuronal injury, shows promise in distinguishing neurodegenerative disorders from psychiatric conditions. This is especially relevant in psychosis, given neurological conditions such as autoimmune encephalitis and Niemann Pick Type C disease (NPC) may initially present with psychotic symptoms. Whilst NfL levels have been studied in established schizophrenia cases, their levels in first-episode psychosis (FEP) and ultra-high risk (UHR) for psychosis individuals remain largely unexplored. This study aimed to compare plasma NfL in people with FEP or UHR with healthy controls, as well as explore its associations with clinical data. We retrospectively analysed plasma NfL in 63 participants, consisting of 29 individuals with FEP, 10 individuals with UHR, and 24 healthy controls. We used general linear models (GLM), which were bootstrapped, to compute bias-corrected and accelerated (BCa) 95 % confidence intervals (CIs). Mean NfL levels were 5.2 pg/mL in FEP, 4.9 pg/mL in UHR, and 5.9 pg/mL in healthy controls. Compared to healthy controls, there were no significant differences in NfL levels in the FEP group (β = −0.22, 95 % CI [−0.86, 0.39], p = 0.516) nor UHR group (β = −0.37, 95 % CI [−0.90, 0.19], p = 0.182). There were no significant associations between NfL levels and clinical variables in the FEP group. Our study is the first to demonstrate that plasma NfL levels are not significantly elevated in individuals at UHR for psychosis compared to healthy controls, a finding also observed in the FEP cohort. These findings bolster the potential diagnostic utility of NfL in differentiating between psychiatric and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

The current paper assessed bradyphrenia, or slowed thinking, in patients with Parkinson's disease, Huntington's disease, and schizophrenia using a modified planning measure designed to maximise the demands on cognitive processing. Findings indicated normal performance in schizophrenia but prolonged thinking time in Parkinson's disease and, to a lesser degree, Huntington's disease and a relationship between thinking time and task complexity. [ABSTRACT FROM AUTHOR]

Background: Many cognitive functions are under strong genetic control and twin studies have demonstrated genetic overlap between some aspects of cognition and schizophrenia. How the genetic relationship between specific cognitive functions and schizophrenia is influenced by IQ is currently unknown. Methods: We applied selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to examine the heritability of specific cognitive functions and associations with schizophrenia liability. Verbal and performance IQ were estimated using The Wechsler Adult Intelligence Scale-III and the Danish Adult Reading Test. In total, 214 twins including monozygotic (MZ = 32) and dizygotic (DZ = 22) pairs concordant or discordant for a schizophrenia spectrum disorder, and healthy control pairs (MZ = 29, DZ = 20) were recruited through the Danish national registers. Additionally, eight twins from affected pairs participated without their sibling. Results: Significant heritability was observed for planning/spatial span (h2 = 25%), self-ordered spatial working memory (h2 = 64%), sustained attention (h2 = 56%), and movement time (h2 = 47%), whereas only unique environmental factors contributed to set-shifting, reflection impulsivity, and thinking time. Schizophrenia liability was associated with planning/spatial span (rph = −0.34), self-ordered spatial working memory (rph = −0.24), sustained attention (rph = −0.23), and set-shifting (rph = −0.21). The association with planning/spatial span was not driven by either performance or verbal IQ. The remaining associations were shared with performance, but not verbal IQ. Conclusions: This study provides further evidence that some cognitive functions are heritable and associated with schizophrenia, suggesting a partially shared genetic etiology. These functions may constitute endophenotypes for the disorder and provide a basis to explore genes common to cognition and schizophrenia. [ABSTRACT FROM AUTHOR]

The article offers information on several longitudinal studies which examined the structural magnetic resonance imaging (MRI) and neurocognitive profiles of individuals at ultra-high risk (UHR) for developing psychosis. One study observed that the grey matter of individuals at high-risk who converted to psychosis showed loss in left inferior frontal, medial temporal and inferior temporal regions. Similar changes were reported in an another study. The neuropsychological functioning of UHR patients was also assessed to examine neurocognitive processes.

• Maternal level of hs-CRP was associated with risk of ADHD the offspring at age 10. • Maternal level of hs-CRP also associated with ADHD symptoms in the entire cohort. • Our rich clinical, population-based data allowed for extensive confounder adjustment. • Maternal pregnancy hs-CRP levels may be a marker of ADHD risk. Maternal inflammation during pregnancy may affect early neurodevelopment in offspring as suggested by preclinical and register data. However, clinical evidence for risk of aberrant neurodevelopment later in childhood is scarce. In the population-based COPSAC 2010 mother–child cohort, we investigated associations between maternal inflammation levels during pregnancy and the risk of a diagnosis of ADHD as well as the load of ADHD symptoms in the children at age 10. The COPSAC 2010 cohort consists of 700 mother–child pairs followed prospectively since pregnancy week 24. Maternal high-sensitivity C-Reactive Protein (hs-CRP) level at week 24 of gestation was investigated in relation to child neurodevelopment by age 10 using logistic and linear regression models with extensive confounder adjustment, including socioeconomic status and maternal polygenic risk of ADHD. The children completed a comprehensive examination of neurodevelopment including categorical (i.e., diagnostic) and dimensional (i.e., symptom load) psychopathology using the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and parental rated ADHD-Rating Scale (ADHD-RS). A total of 604 (86 %) of the 700 children in the COPSAC 2010 cohort participated in the COPSYCH visit at age 10. Sixty-five (10.8 %) fulfilled a research diagnosis of ADHD (16 girls and 49 boys). Higher maternal hs-CRP level in pregnancy at week 24 (median 5.4 mg/L) was significantly associated with increased risk for a diagnosis of ADHD, adjusted OR 1.40, 95 %CI (1.16–1.70), p = 0.001. Additionally, higher maternal hs-CRP was associated with increased ADHD symptom load in the entire cohort, reflected by ADHD-RS raw scores. These clinical data demonstrated a robust association of prenatal maternal inflammation assessed by hs-CRP with a diagnosis of ADHD by age 10. Moreover, maternal inflammation was associated with ADHD symptom load in the complete cohort. Identifying inflammation as an important marker will provide a potential target for future increased awareness and prevention during pregnancy thereby ultimately improving neurodevelopmental outcomes in children. [ABSTRACT FROM AUTHOR]

Background: Empathy is a multidimensional construct, which includes cognitive and affective components. Studies in adults have demonstrated that both cognitive and affective empathy are associated with anxious and depressive symptoms. The aim of this study was to examine these associations in childhood.Methods: Participants were 127 9- and 10-year-old children, recruited from the community. Self-report measures of cognitive and affective empathy, and internalizing symptoms were administered, as well as a task-based measure of cognitive empathy.Results: Canonical correlation analysis demonstrated that components of affective empathy, specifically affective sharing and empathic distress, were associated with internalizing (particularly social anxiety) symptoms (Rc = 0.63, non-parametric p < .001). Cognitive empathy was not associated with internalizing symptoms.Limitations: Most of our findings were based around self-report measures of empathy, which may not accurately reflect empathy ability.Conclusions: Findings suggests that children who share each other's emotions strongly are more likely to experience anxiety, particularly of a social nature. [ABSTRACT FROM AUTHOR]

Objectives: Childhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorders, there is evidence that trauma is associated with an admixture of affective, anxiety and psychotic symptoms in adults. Given that early onset of mental disorder and trauma exposure herald poor outcomes, it is important to examine trauma prevalence rates in youth mental health services and to determine whether this trauma-related clustering is present in help-seeking young people. Methods: We used data from the Transitions Study, a longitudinal investigation of young people attending headspace youth mental health services in Australia between January 2011 and August 2012. Participants were 775 young people aged 12–25. Childhood trauma was assessed using the Childhood Trauma Questionnaire. Multinomial regression was used to assess whether reported childhood trauma was more strongly associated with the co-occurrence of depression, anxiety, mania and psychosis symptoms than with any one in isolation. Results: Approximately 84% of participants reported some form of abuse (emotional: 68%; physical: 32%; sexual: 22%) or neglect (emotional: 65%; physical: 46%). Exposure to multiple trauma types was common. Childhood trauma was significantly associated with each symptom domain. More severe childhood trauma was more strongly associated with the co-occurrence of symptoms than with any one symptom domain in isolation, such that more severely trauma-exposed young people were more likely to experience increased symptom clustering. Conclusions: Childhood trauma is pervasive in youth mental health services and associated with a symptom profile that cuts across traditional diagnostic boundaries. [ABSTRACT FROM AUTHOR]

Multiple lines of research support the dysconnectivity hypothesis of schizophrenia. However, findings on white matter (WM) alterations in patients with schizophrenia are widespread and non-specific. Confounding factors from magnetic resonance image (MRI) processing, clinical diversity, antipsychotic exposure, and substance use may underlie some of the variability. By application of refined methodology and careful sampling, we rectified common confounders investigating WM and symptom correlates in a sample of strictly antipsychotic-naïve first-episode patients with schizophrenia. Eighty-six patients and 112 matched controls underwent diffusion MRI. Using fixel-based analysis (FBA), we extracted fibre-specific measures such as fibre density and fibre-bundle cross-section. Group differences on fixel-wise measures were examined with multivariate general linear modelling. Psychopathology was assessed with the Positive and Negative Syndrome Scale. We separately tested multivariate correlations between fixel-wise measures and predefined psychosis-specific versus anxio-depressive symptoms. Results were corrected for multiple comparisons. Patients displayed reduced fibre density in the body of corpus callosum and in the middle cerebellar peduncle. Fibre density and fibre-bundle cross-section of the corticospinal tract were positively correlated with suspiciousness/persecution, and negatively correlated with delusions. Fibre-bundle cross-section of isthmus of corpus callosum and hallucinatory behaviour were negatively correlated. Fibre density and fibre-bundle cross-section of genu and splenium of corpus callosum were negative correlated with anxio-depressive symptoms. FBA revealed fibre-specific properties of WM abnormalities in patients and differentiated associations between WM and psychosis-specific versus anxio-depressive symptoms. Our findings encourage an itemised approach to investigate the relationship between WM microstructure and clinical symptoms in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3′-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016–1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology. [ABSTRACT FROM AUTHOR]

• Inflammation in schizophrenia may be related to heterogeneous mechanistic pathways. • IL-6 and IL-8 have the most widespread neuroanatomical impact. • IFN-γ plays a potentially protective role in schizophrenia. • Advanced semi-supervised machine-learning techniques can aid detection of inflammation subgroups based on peripheral, accessible blood-based biomarkers. Immune system dysfunction is hypothesised to contribute to structural brain changes through aberrant synaptic pruning in schizophrenia. However, evidence is mixed and there is a lack of evidence of inflammation and its effect on grey matter volume (GMV) in patients. We hypothesised that inflammatory subgroups can be identified and that the subgroups will show distinct neuroanatomical and neurocognitive profiles. The total sample consisted of 1067 participants (chronic patients with schizophrenia n = 467 and healthy controls (HCs) n = 600) from the Australia Schizophrenia Research Bank (ASRB) dataset, together with 218 recent-onset patients with schizophrenia from the external Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism (BeneMin) dataset. HYDRA (HeterogeneitY through DiscRiminant Analysis) was used to separate schizophrenia from HC and define disease-related subgroups based on inflammatory markers. Voxel-based morphometry and inferential statistics were used to explore GMV alterations and neurocognitive deficits in these subgroups. An optimal clustering solution revealed five main schizophrenia groups separable from HC: Low Inflammation, Elevated CRP, Elevated IL-6/IL-8, Elevated IFN-γ, and Elevated IL-10 with an adjusted Rand index of 0.573. When compared with the healthy controls, the IL-6/IL-8 cluster showed the most widespread, including the anterior cingulate, GMV reduction. The IFN-γ inflammation cluster showed the least GMV reduction and impairment of cognitive performance. The CRP and the Low Inflammation clusters dominated in the younger external dataset. Inflammation in schizophrenia may not be merely a case of low vs high, but rather there are pluripotent, heterogeneous mechanisms at play which could be reliably identified based on accessible, peripheral measures. This could inform the successful development of targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma, particularly sexual abuse, has been associated with transition to psychosis in individuals at "ultra-high risk" (UHR). This study investigated whether the effects of various forms of childhood trauma on transition to psychosis are mediated by cortical thickness and surface area abnormalities.Methods: This prospective study used data from 62 UHR individuals from a previous (PACE 400) cohort study. At follow-up, 24 individuals had transitioned to psychosis (UHR-T) and 38 individuals had not transitioned (UHR-NT). Student-t/Mann-Whitney-U tests were performed to assess morphological differences in childhood trauma (low/high) and transition. Mediation analyses were conducted using regression and bootstrapping techniques.Results: UHR individuals with high sexual trauma histories presented with decreased cortical thickness in bilateral middle temporal gyri and the left superior frontal gyrus compared to those with low sexual trauma. Participants with high physical abuse had increased cortical thickness in the right middle frontal gyrus compared to those with low physical abuse. No differences were found for emotional abuse or physical/emotional neglect. Reduced cortical thickness in the right middle temporal gyrus and increased surface area in the right cingulate were found in UHR-T compared to UHR-NT individuals. Sexual abuse had an indirect effect on transition to psychosis, where decreased cortical thickness in the right middle temporal gyrus was a mediator.Conclusions: Results suggest that childhood sexual abuse negatively impacted on cortical development of the right temporal gyrus, and this heightened the risk of transition to psychosis in our sample. Further longitudinal studies are needed to precisely understand this link. [ABSTRACT FROM AUTHOR]

Background: Anorexia nervosa (AN) is a potentially fatal psychiatric condition, associated with structural brain changes such as gray matter volume loss. The pathophysiological mechanisms for these changes are not yet fully understood. Iron is a crucial element in the development and function of the brain. Considering the systemic alterations in iron homeostasis in AN, we hypothesized that brain iron would be altered as a possible factor associated with structural brain changes in AN. Methods: In this study, we used quantitative susceptibility mapping (QSM) magnetic resonance imaging to investigate brain iron in current AN (c-AN) and weight-restored AN compared with healthy individuals. Whole-brain voxel wise comparison was used to probe areas with possible group differences. Further, the thalamus, caudate nucleus, putamen, nucleus accumbens, hippocampus, and amygdala were selected as the regions of interest (ROIs) for ROI-based comparison of mean QSM values. Results: Whole-brain voxel-wise and ROI-based comparison of QSM did not reveal any differences between groups. Exploratory analyses revealed a correlation between higher regional QSM (higher iron) and lower body mass index, higher illness severity, longer illness duration, and younger age at onset in the c-AN group. Conclusions: This study did not find evidence of altered brain iron in AN compared to healthy individuals. However, the correlations between clinical variables and QSM suggest a link between brain iron and weight status or biological processes in AN, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Highlights • 15% of the child abuse instruments had strong to moderate levels of evidence. • No instruments had adequate levels of evidence for all COSMIN criteria. • No single instrument is superior to all others across settings and populations. • Measures that capture the effects child abuse on brain development are limited. Abstract Child abuse is a major public health concern and a strong predictor of adult psychopathology. However, a consensus on how best to measure child abuse is not evident. This review aimed to critically appraise the methodological quality and measurement properties of published child abuse measures, examined the strength of evidence of these instruments for research use using the COnsensus-based Standards for the selection of health Measurement InstrumeNts (COSMIN) checklist and determined which measures were capable of providing information on the developmental timing of abuse. Systematic search of electronic databases identified 52 eligible instruments from 2095 studies. Only 15% (n = 8) of the instruments had strong to moderate levels of evidence for three or more of the nine COSMIN criteria. No instrument had adequate levels of evidence for all criteria, and no criteria were met by all instruments. Our results indicate there is no single instrument that is superior to all others across settings and populations. The availability of measures capable of capturing the effects of child abuse on brain development and associated behavioral phenotypes are limited. Refined instruments with a focus on capturing abuse events during development are warranted in addition to further evaluation of the psychometric properties of these instruments. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The International Society for Bipolar Disorders-Battery for Assessment of Neurocognition (ISBD-BANC)," by L. N. Yatham and colleagues in the 2010 issue.

The article offers information about dystonia. The term was introduced in 1911 by Oppenheim, to describe the variable muscular tone noted in patients experiencing abnormal muscle spasms. In essence, dystonia describes a syndrome of sustained muscle contractions that produce abnormal postures or repetitive movements.

The article offers information on catatonia. This motor syndrome has been linked with schizophrenia and akinesia. It motor symptoms are similar to that of depression, mania, encephalitis lethargica, third ventricle-related tumors, seizures and Wilson's disease. Advances in mental health and the growth of antipsychotics have a negative impact on the diagnosis of catatonia.

Reports a case in which a decrease in the white cell count occurred due to the adjunctive use of sodium valproate and clozapine. Risks of neutropaenia and agranulocytosis; Pros and cons of using sodium valproate in conjunction with clozapine to treat schizophrenia.

Presents case studies of patients with clozapine-resistant schizophrenia treated with risperidone. Symptoms of the disorder; Efficacy of risperidone; Dosage of risperidone.

Autism spectrum disorders (ASD) are associated with cognitive dysfunctions, including mental time travel (MTT). However, findings on diminished MTT ability may be confounded by a number of factors, including the individuals' language ability, factors related to the MTT task and the demographic factors of participants. The present study provided a meta-analysis of MTT ability in people with ASD. The results showed significant overall reductions in MTT ability in people with ASD. Moderator analyses revealed that the variables examined did not explain the reduction in MTT ability. These findings suggest that MTT ability is diminished in people with ASD and that the degree of this diminishment may not depend on the characteristics of measures or demographic variables of people with ASD. [ABSTRACT FROM AUTHOR]

This letter, published in the Indian Journal of Psychological Medicine, discusses the use of erythromycin as a treatment for clozapine-induced constipation. Clozapine, a medication used to treat treatment-resistant schizophrenia, can cause gastrointestinal hypomotility, leading to severe constipation and bowel obstruction. The usual management for this condition is the administration of laxatives, but their efficacy is uncertain. The authors report a case where erythromycin was successfully used as an adjunctive treatment to restart clozapine in a patient with constipation. They suggest that erythromycin may be an effective strategy for managing clozapine-induced constipation and should be further investigated in clinical trials. [Extracted from the article]

Despite a growing body of research, there is yet to be a cohesive synthesis of studies examining differences in brain morphology according to patterns of cognitive function among both schizophrenia-spectrum disorder (SSD) and bipolar disorder (BD) individuals. We aimed to provide a systematic overview of the morphological differences—inclusive of grey and white matter volume, cortical thickness, and cortical surface area—between cognitive subgroups of these disorders and healthy controls, and between cognitive subgroups themselves. An initial search of PubMed and Scopus databases resulted in 1486 articles of which 20 met inclusion criteria and were reviewed in detail. The findings of this review do not provide strong evidence that cognitive subgroups of SSD or BD map to unique patterns of brain morphology. There is preliminary evidence to suggest that reductions in cortical thickness may be more strongly associated with cognitive impairment, whilst volumetric deficits may be largely tied to the presence of disease. [ABSTRACT FROM AUTHOR]