Early Stages Of Psychosis Research Articles

Thalamocortical Anatomical Connectivity in Schizophrenia and Psychotic Bipolar Disorder

Background Anatomical connectivity between the thalamus and cortex, including the prefrontal cortex (PFC), is abnormal in schizophrenia. Overlapping phenotypes, including deficits in executive cognitive abilities dependent on PFC-thalamic circuitry, suggest dysrupted thalamocortical anatomical connectivity may extend to psychotic bipolar disorder. We tested this hypothesis and examined the impact of illness stage to inform when in the illness course thalamocortical dysconnectivity emerges. Methods Diffusion-weighted imaging data were collected on 70 healthy individuals and 124 people with a psychotic disorder (schizophrenia spectrum = 75; psychotic bipolar disorder = 49), including 62 individuals in the early stage of psychosis. Anatomical connectivity between major divisions of the cortex and thalamus was quantified using probabilistic tractography and compared between groups. Associations between PFC-thalamic anatomical connectivity and executive cognitive abilities were examined using regression analysis. Results Psychosis was associated with lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity. Follow-up analyses established that lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity were present in both schizophrenia and psychotic bipolar disorder. Lower PFC-thalamic anatomical connectivity was also present in early-stage and chronic psychosis. Contrary to expectations, lower PFC-thalamic anatomical connectivity was not associated with impaired executive cognitive abilities. Conclusions Altered thalamocortical anatomical connectivity, especially reduced PFC-thalamic connectivity, is a transdiagnostic feature of psychosis detectable in the early stage of illness. Further work is required to elucidate the functional consequences of the full spectrum of thalamocortical connectivity abnormalities in psychosis.

Modelling Dynamic Changes in Thalamo-Cortical and Thalamo-Cerebellar Functional Connectivity in the Early Stage of Psychosis

Modelling Dynamic Changes in Thalamo-Cortical and Thalamo-Cerebellar Functional Connectivity in the Early Stage of Psychosis

Hierarchical Symptom Factors in Early Psychosis

Quantitative models of psychopathology can empirically guide sub-classification of heterogeneous clinical presentations such as psychosis and are particularly well-equipped to capture the nuanced symptomatology observed in first-episode psychosis. As well, factors may be better aligned to biological variables. Kotov et al. (2016) performed a hierarchical factor analysis of psychosis symptoms first-admission, and linked symptoms to longitudinal disability and event-related potentials. The current study sought to replicate their factor analysis results in outpatients with early stage psychosis.

Relational Memory in Early Psychosis: A 2 Year Follow-Up Study

Relational memory, or the ability to bind information into complex memories, is substantially impaired in schizophrenia. Lesser impairments have been demonstrated in early-stage psychosis, suggesting relational memory progressively worsens throughout illness. Relational memory declines are thought to parallel progressive impairment in hippocampal function, suggesting relational memory may be a target for early cognitive intervention. However, the window for intervention remains unclear, as no studies to date have assessed relational memory longitudinally in early psychosis.

Thalamocortical Anatomical Connectivity in Schizophrenia and Psychotic Bipolar Disorder

Anatomical connectivity between the thalamus and cortex, including the prefrontal cortex (PFC), is abnormal in schizophrenia. Overlapping phenotypes, including deficits in executive cognitive abilities dependent on PFC-thalamic circuitry, suggest dysrupted thalamocortical anatomical connectivity may extend to psychotic bipolar disorder. We tested this hypothesis and examined the impact of illness stage to inform when in the illness course thalamocortical dysconnectivity emerges. Diffusion-weighted imaging data were collected on 70 healthy individuals and 124 people with a psychotic disorder (schizophrenia spectrum = 75; psychotic bipolar disorder = 49), including 62 individuals in the early stage of psychosis. Anatomical connectivity between major divisions of the cortex and thalamus was quantified using probabilistic tractography and compared between groups. Associations between PFC-thalamic anatomical connectivity and executive cognitive abilities were examined using regression analysis. Psychosis was associated with lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity. Follow-up analyses established that lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity were present in both schizophrenia and psychotic bipolar disorder. Lower PFC-thalamic anatomical connectivity was also present in early-stage and chronic psychosis. Contrary to expectations, lower PFC-thalamic anatomical connectivity was not associated with impaired executive cognitive abilities. Altered thalamocortical anatomical connectivity, especially reduced PFC-thalamic connectivity, is a transdiagnostic feature of psychosis detectable in the early stage of illness. Further work is required to elucidate the functional consequences of the full spectrum of thalamocortical connectivity abnormalities in psychosis.

Lipides membranaires dans la schizophrénie et la psychose débutante : de potentiels biomarqueurs et pistes thérapeutiques ?

The various roles of membrane lipids in human health has urged researchers to study their impact in neuropsychiatric diseases, especially in schizophrenia spectrum disorders and more recently in early stages of psychosis. The progress in mass spectrometry technologies now allows a more comprehensive analysis of phospholipids (PL) and their fatty acid (FA) molecular species. FA are defined by a carbon chain of variable length and are said to be unsaturated when their chain has one or more carbon-carbon double bonds. The PL are composed of a hydrophilic polar head with a phosphoric acid group and an hydrophobic part with FAs; they encompass glycerophospholipids and sphingolipids. The plasma membrane is a complex and dynamic structure consisting of a lipid bilayer composed of an outer layer and an inner layer of specific lipid composition. The permanent remodeling of membrane lipids involves phospholipases especially the phospholipase A2. Seventy percent of the brain consists of lipids from different classes and molecular species. Most of the brain lipids are composed of polyunsaturated fatty acid (PUFA)-enriched diacyl classes where omega-3 and omega-6 molecular species predominate. The balance between omega-3 and omega-6 is important for the neurodevelopment. PUFA are also involved in neurogenesis and neurotransmission. Sphingomyelin (SM) is a sphingolipid that influences inflammation, cell proliferation and lipid rafts formation. It is an important component of myelin sheaths of white matter and therefore is involved in cerebral connectivity. In rat models, deficiency in omega-3 causes abnormalities in dopaminergic neurotransmission, impacts on the functioning of some receptors (including cannabinoids CB1, glutamatergic N-methyl-D-aspartate receptor, NMDA), and increases sensitivity to hallucinogens. In contrast, omega-3 supplementation improves cognitive function and prevents psychotic-like behavior in some animal models for schizophrenia. It also reduces oxidative stress and prevents demyelination. The historical membrane hypothesis of schizophrenia has led to explore the lipids abnormality in this disorder. This hypothesis was initially based on the observation of an abnormal membrane prostaglandin production in schizophrenia caused by a membrane arachidonic acid deficiency. It has evolved emphasizing the various PUFA membrane's roles in particular regarding oxidative stress, inflammation and regulation of the NMDA receptors. In patients with mental disorders, low omega-3 index is more frequent than in the general population. This lipid abnormality could lead to myelination abnormalities and cognitive deficits observed in patients. It could also participate in oxidative stress abnormalities and inflammation reported in schizophrenia. On the other hand, low omega-3 index deficit was reported to be associated with an increased cardiovascular risk, and omega-3 supplementation may also have a positive cardiovascular impact in psychiatric patients, even more than in the general population. The presence of membrane lipid abnormalities is also found in patients during the first psychotic episode (FEP). The omega-3 supplementation improved the recovery rate and prevented the loss of gray matter in FEP. In patients at ultra-high risk to develop a psychotic disorder (UHR), omega-3 supplementation has been associated with a reduction of the rate of conversion to psychosis and with metabolic changes, such as decreased activity of phospholipase A2. However, this study has not as yet been replicated. Not all patients exhibit lipid abnormalities. Several studies, including studies from our team, have found a bimodal distribution of lipids in patients with schizophrenia. But some studies have found differences (in PUFA) in the acute phase whereas our studies (on phospholipids) are in chronic phases. It will be interesting to study in more depth the links between these two parameters. Furthermore, we identified a subgroup which was identified with a deficit in sphingomyelin and PUFA whereas others have found an increase of sphingomyelin. Individuals with this abnormal lipid cluster had more cognitive impairments and more severe clinical symptoms. Because the niacin test is an indirect reflection of arachidonic acid levels, it has been proposed to identify a subset of patients with membrane lipids anomalies. Niacin test response is influenced by several factors related to lipid metabolism, including cannabis use and phospholipase A2 activity. Despite progress, the function and impact of membrane lipids are still poorly understood in schizophrenia. They could serve as biomarkers for identifying biological subgroups among patients with schizophrenia. In UHR patients, their predictive value on the conversion to psychosis should be tested. Omega-3 supplementation could be a promising treatment thanks to its good tolerance and acceptability. It could be more appropriate for patients with PUFA anomalies in a more personalized medical approach.

Suicidal thoughts and behavior (STB) and psychosis-risk symptoms among psychiatrically hospitalized adolescents

BackgroundIndividuals in the early stages of psychosis have a markedly high risk for suicidal thoughts and behavior (STB). It is not well understood if STB among those with psychosis-risk symptoms is accounted for by co-occurring psychopathology (e.g., depression), unique experiences specific to psychosis-spectrum symptomatology (e.g., hallucinations, delusions), or combined effects of different factors. This cross-sectional study explored the link between psychosis-spectrum symptoms, co-occurring disorders, and STB. MethodsThis record review included 569 adolescents (mean age = 14.83) admitted to a psychiatric inpatient hospital due to exhibiting behavior indicating they were an imminent threat to themselves or others. Upon intake to the hospital, participants completed a diagnostic interview and self-report measures of suicidal ideation, suicide attempt history, and psychosis-spectrum symptoms. The primary analysis used linear regression to predict suicidal ideation from psychosis-spectrum symptom scores, controlling for known characteristics associated with STB including specific psychiatric disorders (i.e. depressive, anxiety, post-traumatic stress, and psychotic disorders), biological sex, and race. ResultsPsychosis-spectrum symptoms predicted suicidal ideation above and beyond the significant effects of a depressive disorder diagnosis and sex, as well as the non-significant effects of anxiety, PTSD, full-threshold psychosis, and race. Item-level correlations demonstrated that several psychosis-spectrum symptoms were significantly associated with ideation and lifetime suicide attempts. ConclusionsResults indicate that within this sample of psychiatrically hospitalized youth, psychosis-risk symptoms were uniquely linked to STB. These findings suggest that attention to psychosis-spectrum symptoms, including several specific psychosis-risk experiences, may be clinically important for better assessment and treatment of suicidal youth.

Adolescents at clinical high risk for psychosis show qualitatively altered patterns of activation during rule learning

BackgroundThe ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis. Methods24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules. ResultsPrevious work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding. ConclusionsThese findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression.

Jumping to social conclusions?: The implications of early and uninformed social judgements in first episode psychosis.

Although social cognition is now understood to be a key determinant of functional outcome in psychosis, the factors associated with impaired performance on tasks of social cognition still remain unclear. Jumping to conclusions (JTC) is a cognitive bias that is commonly observed in psychosis, and features of this bias may be implicated in the accurate processing of social information. In the present study, a sample of patients in the early stages of psychosis (n = 35) and demographically matched community controls (n = 35) were presented with a modified version of the Interpersonal Perception Task in which video clips of naturalistic social scenarios were paused at 3 predetermined time points. All participants were prompted to answer a series of questions during these time points to examine the processes by which individuals arrive at social judgments. A JTC response pattern was defined as endorsing overconfident responses and a low need for additional social information at the beginning time points of the video clips when limited social cues were available. Compared with controls, a greater proportion of patients exhibited a response pattern suggestive of JTC, which was also strongly associated with poorer overall task accuracy, regardless of group status. Results from this study provide evidence that overconfidence in premature and uninformed social judgments has direct consequences for the accurate processing of social information. Furthermore, this response pattern, which was more characteristic of early psychosis patients, may represent JTC in real-world social contexts, and could be an important therapeutic target for social cognition in the early stages of illness. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Grey-matter abnormalities in clinical high-risk participants for psychosis

The current study examined the presence of abnormalities in cortical grey-matter (GM) in a sample of clinical high-risk (CHR) participants and examined relationships with psychosocial functioning and neurocognition. CHR-participants (n = 114), participants who did not fulfil CHR-criteria (CHR-negative) (n = 39) as well as a group of healthy controls (HC) (n = 49) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed. No significant differences in GM-thickness and intensity were observed in CHR-participants compared to CHR-negative and HC. Circumscribed abnormalities in GM-intensity were found in the visual and frontal cortex of CHR-participants. Moreover, small-to-moderate correlations were observed between GM-intensity and neuropsychological deficits in the CHR-group. The current data suggest that CHR-participants may not show comprehensive abnormalities in GM. We discuss the implications of these findings for the pathophysiological theories of early stage-psychosis as well as methodological issues and the impact of different recruitment strategies.

Implementing MR Imaging into Clinical Routine Screening in Patients with Psychosis?

MR imaging is a suitable instrument for the detection of incidental radiological findings in patients with early psychosis and guidance of subsequent treatment adjustments. We outline evidence showing the clinical utility of MR imaging to guide treatment selection by identifying radiological abnormalities and predicting clinical outcomes in early-stage psychosis. We argue that MR imaging is an indispensable screening tool to detect gross radiological abnormalities in early psychosis and implementation in routine clinical assessments is warranted. We highlight future key challenges and make pragmatic suggestions to exploit the potential of MR imaging to construct robust prognostic models for personalized early interventions.

Patterns and perceptions of face-to-face and digital communication in the clinical high risk and early stages of psychosis

Digital communication can mitigate some of the challenges inherent in face-to-face communication; however, it is unclear whether this communication format is preferred among youth with emerging psychosis. Therefore, we examined characteristics of face-to-face and digital communication in youth at clinical high risk for psychosis (CHR; n = 19) or in the first episode of psychosis (FEP; n = 57), as well as age-matched community comparisons (n = 51). Participants completed a 25-item self-report questionnaire to assess between- and within-group differences in the frequency of, satisfaction with, and barriers to face-to-face and digital communication. Compared to controls, both clinical groups endorsed a lower frequency of face-to-face and digital interactions across a range of communication partners. Controls reported higher satisfaction and fewer challenges with both communication formats than CHR and FEP groups. No between-group differences were identified among clinical participants in characteristics of face-to-face and digital interactions. Youth at clinical high risk for, or in the first episode of, psychosis exhibited similar communication patterns and perceptions that significantly diverged from community controls. These findings highlight that reductions in the quality and quantity of social interactions extend to digital contexts, and that both communication formats are relevant clinical targets in the high risk and early stages of psychosis.

Reward anticipation in individuals with subclinical psychotic experiences: A functional MRI approach

Previous research in patients with psychotic disorder has shown widespread abnormalities in brain activation during reward anticipation. Research at the level of subclinical psychotic experiences in individuals unexposed to antipsychotic medication is limited with inconclusive results. Therefore, brain activation during reward anticipation was examined in a larger sample of individuals with subclinical psychotic experiences (PE). Participants in the PE-group were included based on CAPE scores. A sample of emerging adults aged 16–26 years (n = 47) with PE and healthy controls (HC) (n = 40) underwent fMRI scanning. The Monetary Incentive Delay task was conducted with cues related to win, loss or neutral conditions. fMRI nonparametric tests were used to examine the reward versus neutral cue contrast. A significant main effect of the large win (€3.00) > neutral contrast was found in both groups showing activation in many brain areas, including classic reward regions. Whole brain analysis on the group comparison regarding the large win > neutral contrast showed significantly decreased activation in the right insula, putamen and supramarginal gyrus in the PE-group compared to controls. There was no group difference in the hypothesized reward-related region. Decreased activation in the right insula, putamen and supramarginal gyrus during reward anticipation in individuals with PE may be consistent with altered processing of sensory information, related to decreased emotional valuing and motivational tendencies and/or altered motor-cognitive processes. The absence of group differences in striatal activation suggests that activation here is intact in the earliest stages of psychosis and may exhibit progressive deterioration in as the disease develops.

Hyperactivity and Reduced Activation of Anterior Hippocampus in Early Psychosis.

In schizophrenia, the anterior hippocampus is hyperactive and shows reduced task-related recruitment, but the relationship between these two findings is unclear. The authors tested the hypothesis that hyperactivity impairs recruitment of the anterior hippocampus during scene processing. Functional MRI data from 45 early-psychosis patients and 35 demographically matched healthy control subjects were analyzed using a block-design 1-back scene-processing task. Hippocampal activation in response to scenes and faces compared with scrambled images was measured. In a subset of 20 early-psychosis patients and 31 healthy control subjects, baseline hippocampal activity using cerebral blood volume (CBV) mapping was measured. Correlation analyses were used to examine the association between baseline hippocampal activity and task-related hippocampal activation. Activation of the anterior hippocampus was significantly reduced and CBV in the anterior hippocampus was significantly increased in the early stages of psychosis. Increased CBV in early-psychosis patients was inversely correlated with task-related activation during scene processing in the anterior hippocampus. Anterior hippocampal hyperactivity in early-psychosis patients appears to limit effective recruitment of this region during task performance. These findings provide novel support for the anterior hippocampus as a therapeutic target in the treatment of cognitive deficits in psychosis.

Relatives' attachment anxiety mediates the association between perceived loss and expressed emotion in early psychosis.

A common reaction experienced by family members of patients with psychosis is grief for the loss of their healthy relative. Importantly, high levels of perceived loss have been related to the manifestation of high expressed emotion (EE), which includes the negative attitudes expressed by relatives toward an ill family member. However, the mechanisms underlying the relationship between relatives’ perceived loss and EE attitudes in the early stages of psychosis are still not fully understood. In this regard, attachment theory has been suggested as a useful framework for understanding this link. The current study aimed to examine: (1) whether relatives’ perceived loss was associated with relatives’ EE dimensions (i.e., criticism and emotional over-involvement (EOI)), and (2) whether such associations were mediated by relatives’ attachment dimensions (i.e., anxiety and avoidance). Seventy-eight relatives of patients with early psychosis completed the Mental Illness Version of the Texas Inventory of Grief for the assessment of loss reactions. Attachment dimensions and EE attitudes were assessed by the Psychosis Attachment Measure and the Family Questionnaire, respectively. Findings indicated that relatives’ perceived loss was associated with EE dimensions. Relatives’ attachment anxiety, but not avoidance, mediated the relationship of perceived loss with both criticism and EOI. Findings highlight the importance of examining the role of relatives’ attachment characteristics for understanding how perceptions of loss might impact the manifestation of EE attitudes in the early stages of psychosis. Family interventions aimed at assisting relatives to improve their management of negative emotional reactions to loss are fundamental to prevent impairing loss reactions and the entrenchment of high-EE attitudes.

Altered syntactic abilities in first episode patients: An inner phenomenon characterizing psychosis

BackgroundResearch has consistently shown that language abilities represent a core dimension of psychosis; however, to date, very little is known about syntactic comprehension performance in the early stages of psychosis. This study aims to compare the linguistic abilities involved in syntactic comprehension in a large group of First Episode Psychosis (FEP) patients and healthy controls (HCs). MethodsA multiple choice test of comprehension of syntax was administered to 218 FEP patients (166 non-affective FEP patients [FEP-NA] and 52 affective FEP patients [FEP-A]) and 106 HCs. All participants were asked to match a sentence they listen with one out of four vignettes on a pc screen. Only one vignette represents the stimulus target, while the others are grammatical or non-grammatical (visual) distractors. Both grammatical and non-grammatical errors and performance in different syntactic constructions were considered. ResultsFEP committed greater number of errors in the majority of TCGB language domains compared to HCs. Moreover, FEP-NA patients committed significantly more non-grammatical (z = −3.2, p = 0.007), locative (z = −4.7, p < 0.001), passive-negative (z = −3.2, p = 0.02), and relative (z = −4.6, p < 0.001) errors compared to HCs as well as more passive-affirmative errors compared to both HCs (z = −4.3, p < 0.001) and FEP-A (z = 3.1, p = 0.04). Finally, we also found that both FEP-NA and FEP-A committed more grammatical (FEP-NA: z = −9.2, p < 0.001 and FEP-A: z = −4.4, p < 0.001), total (FEP-NA: z = −8.2, p < 0.001 and FEP-A: z = 3.9, p = 0.002), and active-negative (FEP-NA: z = −5.8, p < 0.001 and FEP-A: z = −3.5, p = 0.01) errors compared to HCs. ConclusionsThis study shows that the access to syntactic structures is already impaired in FEP patients, especially in those with FEP-NA, ultimately suggesting that language impairments represent a core and inner feature of psychosis even at early stages.

Towards Precision Medicine in Psychosis: Benefits and Challenges of Multimodal Multicenter Studies-PSYSCAN: Translating Neuroimaging Findings From Research into Clinical Practice.

In the last 2 decades, several neuroimaging studies investigated brain abnormalities associated with the early stages of psychosis in the hope that these could aid the prediction of onset and clinical outcome. Despite advancements in the field, neuroimaging has yet to deliver. This is in part explained by the use of univariate analytical techniques, small samples and lack of statistical power, lack of external validation of potential biomarkers, and lack of integration of nonimaging measures (eg, genetic, clinical, cognitive data). PSYSCAN is an international, longitudinal, multicenter study on the early stages of psychosis which uses machine learning techniques to analyze imaging, clinical, cognitive, and biological data with the aim of facilitating the prediction of psychosis onset and outcome. In this article, we provide an overview of the PSYSCAN protocol and we discuss benefits and methodological challenges of large multicenter studies that employ neuroimaging measures.

Impaired relational memory in the early stage of psychosis

BackgroundHumans constantly take in vast amounts of information, which must be filtered, flexibly manipulated, and integrated into cohesive relational memories in order to choose relevant behaviors. Relational memory is impaired in chronic schizophrenia, which has been linked to hippocampal dysfunction. It is unclear whether relational memory is impaired in the early stage of psychosis. MethodsWe studied eye movements during a face-scene pairs task as an indirect measure of relational memory in 89 patients in the early stage of psychosis and 84 healthy control participants. During testing, scenes were overlaid with three equally-familiar faces and participants were asked to recall the matching (i.e. previously-paired) face. During Match trials, one face had been previously paired with the scene. During Non-Match trials, no faces matched the scene. Forced-choice explicit recognition was recorded as a direct measure of relational memory. ResultsHealthy control subjects rapidly (within 250–500 ms) showed preferential viewing of the matching face during Match trials. In contrast, preferential viewing was delayed in patients in the early stage of psychosis. Explicit recognition of the matching face was also impaired in the patient group. ConclusionsThis study provides novel evidence for a relational memory deficit in the early stage of psychosis. Patients showed deficits in both explicit recognition as well as abnormal eye-movement patterns during memory recall. Eye movements provide a promising avenue for the study of relational memory in psychosis, as they allow for the assessment of rapid, nonverbal memory processes.

Clinical and neurodevelopmental correlates of aggression in early psychosis

BackgroundAlthough mental illness accounts for only 4% of aggressive behavior in the general population, there remains a modest association between aggressive behavior and psychotic disorders, particularly in the early stages of the illness. However, little is known about the specific factors associated to this increased risk. AimsThe present study aims to assess the rates, characteristics and risk factors of aggressive behavior in first episode psychosis patients (FEP). MethodWe conducted a retrospective chart review of 449 FEP patients recruited from an outpatient early psychosis clinic. Aggressive behavior and clinical information were rated based upon information gathered from the chart review of data collected at baseline and after 6 months of follow-up. ResultsRates of aggressive behavior were 54.3% in FEP patients. Aggressive behavior was significantly associated with higher rates of history of birth complications, neurodevelopmental delays, learning difficulties, alcohol use disorders, and the clinical domain of poverty symptoms. In addition to aggressive behavior, 16.7% of FEP patients exhibited suicidal ideation or behaviors and 11.4% exhibited non-suicidal self-injurious behavior (NSSIB). In contrast to baseline, aggressive behaviors at 6 months follow up were almost entirely absent. ConclusionsPatients at early stages of psychosis have high rates of aggressive and suicidal behavior prior to contact with clinical services. Neurodevelopmental adversities, alcohol use disorders and poverty symptoms are associated to higher risk of aggression in early psychosis. Participation in early psychosis specialty care resulted in a dramatic reduction in aggressive behavior.

In Vivo Availability of Cannabinoid 1 Receptor Levels in Patients With First-Episode Psychosis

ImportanceExperimental and epidemiological studies implicate the cannabinoid 1 receptor (CB1R) in the pathophysiology of psychosis. However, whether CB1R levels are altered in the early stages of psychosis and whether they are linked to cognitive function or symptom severity remain unknown.ObjectiveTo investigate CB1R availability in first-episode psychosis (FEP) without the confounds of illness chronicity or the use of illicit substances or antipsychotics.Design, Setting, and ParticipantsThis cross-sectional, case-control study of 2 independent samples included participants receiving psychiatric early intervention services at 2 independent centers in Turku, Finland (study 1) and London, United Kingdom (study 2). Study 1 consisted of 18 volunteers, including 7 patients with affective or nonaffective psychoses taking antipsychotic medication and 11 matched controls; study 2, 40 volunteers, including 20 antipsychotic-naive or antipsychotic-free patients with schizophrenia or schizoaffective disorder and 20 matched controls. Data were collected from January 5, 2015, through September 26, 2018, and analyzed from June 20, 2016, through February 12, 2019.Main Outcomes and MeasuresThe availability of CB1R was indexed using the distribution volume (VT, in milliliters per cubic centimeter) of 2 CB1R-selective positron emission tomography radiotracers: fluoride 18–labeled FMPEP-d2 (study 1) and carbon 11–labeled MePPEP (study 2). Cognitive function was measured using the Wechsler Digit Symbol Coding Test. Symptom severity was measured using the Brief Psychiatric Rating Scale for study 1 and the Positive and Negative Syndrome Scale for study 2.ResultsA total of 58 male individuals were included in the analyses (mean [SD] age of controls, 27.16 [5.93] years; mean [SD] age of patients, 26.96 [4.55] years). In study 1, 7 male patients with FEP (mean [SD] age, 26.80 [5.40] years) were compared with 11 matched controls (mean [SD] age, 27.18 [5.86] years); in study 2, 20 male patients with FEP (mean [SD] age, 27.00 [5.06] years) were compared with 20 matched controls (mean [SD] age, 27.15 [6.12] years). In study 1, a significant main effect of group on [18F]FMPEP-d2 VT was found in the anterior cingulate cortex (ACC) (t16 = −4.48; P < .001; Hedges g = 1.2), hippocampus (t16 = −2.98; P = .006; Hedges g = 1.4), striatum (t16 = −4.08; P = .001; Hedges g = 1.9), and thalamus (t16 = −4.67; P < .001; Hedges g = 1.4). In study 2, a significant main effect of group on [11C]MePPEP VT was found in the ACC (Hedges g = 0.8), hippocampus (Hedges g = 0.5), striatum (Hedges g = 0.4), and thalamus (Hedges g = 0.7). In patients, [11C]MePPEP VT in the ACC was positively associated with cognitive functioning (R = 0.60; P = .01), and [11C]MePPEP VT in the hippocampus was inversely associated with Positive and Negative Syndrome Scale total symptom severity (R = −0.50; P = .02).Conclusions and RelevanceThe availability of CB1R was lower in antipsychotic-treated and untreated cohorts relative to matched controls. Exploratory analyses indicated that greater reductions in CB1R levels were associated with greater symptom severity and poorer cognitive functioning in male patients. These findings suggest that CB1R may be a potential target for the treatment of psychotic disorders.