Predicting psychosis in at-risk patients using abnormal neural oscillations and synchrony in conjunctions with machine learning algorithms

This study investigated patterns of motor brain activation, white matter (WM) integrity of inter- and intrahemispheric connectivity and their associations with hand function in children with unilateral cerebral palsy (CP-U). Fourteen CP-U (mean age 10.6±2.7years) and 14 typically developing children (TDC) underwent magnetic resonance imaging. CP-U underwent extensive motor evaluation. Pattern of brain activation during a motor task was studied in 12 CP-U and six TDC, by calculating laterality index (LI) and percent activation in the sensorimotor areas (around the central sulcus), and quantifying the activation in the supplementary motor area (SMA). Diffusivity parameters were measured in CP-U and eight other TDC for the corpus callosum (CC), affected and less affected cortico-spinal tracts (CST), and posterior limb of the internal capsule (PLIC). Abnormal patterns of brain activation were detected in areas around the central sulcus in 9/12 CP-U, with bilateral activation and/or reduced percent activation. More activation in areas around the central sulcus of the affected hemisphere was associated with better hand function. CP-U demonstrated more activation in the SMA when moving the affected hand compared to the less affected hand. CP-U displayed reduced WM integrity compared to TDC, in the midbody and splenium of the CC, affected CST and affected PLIC. WM integrity in these tracts was correlated with hand function. While abnormal pattern of brain activation was detected mainly when moving the affected hand, the integrity of the CC was correlated with function of both hands and bimanual skills. This study highlights the importance of interhemispheric connectivity for hand function in CP-U, which may have clinical implications regarding prognosis and management.

Aberrant social cognition is a core feature of schizophrenia, persisting from clinical high-risk and genetic high-risk states to the first episode of psychosis. This study aimed to identify shared and distinct social cognition-related functional alterations across clinical high-risk, genetic high-risk, and first episode of psychosis groups, shedding light on varying risk levels for first episode of psychosis development. Meta-analyses were performed on 38 whole-brain task-based functional magnetic resonance imaging studies (12 clinical high risk, 15 genetic high risk, 11 first episode of psychosis) using Seed-based d Mapping. Function abnormalities were assessed within each patient group, with quantitative comparisons made against controls. Clinical high-risk and genetic high-risk individuals showed neither shared nor distinct abnormal brain activation during social cognition tasks. A shared cluster of increased activation in the right anterior cingulate cortex was observed between genetic high-risk and first episode of psychosis groups. However, no conjunction or disjunction results were found between clinical high-risk and first episode of psychosis groups. Meta-regression analyses revealed accelerated age-related greater activation decline in the left insula in individuals with clinical high risk. In conclusion, the absence of shared social cognition-related brain activation between clinical high risk and genetic high risk may signify differences in neural correlates underlying social cognition deficits between these groups and they follow distinct neural pathways toward first episode of psychosis. The shared abnormal anterior cingulate cortex activation in genetic high risk and first episode of psychosis may represent an endophenotype of schizophrenia.

Innovations: Psychoeducation: Multifamily Group Treatment in a Program for Patients With First-Episode Psychosis: Experiences From the TIPS Project

This dissertation contributes with novel predictive modelling approaches to data-driven computational psychiatry and offers alternative analyses frameworks to the standard statistical analyses in psychiatric research. In particular, this document advances research in medical data mining, especially psychiatry, via two phases. In the first phase, this document promotes research by proposing synergistic machine learning and statistical approaches for detecting patterns and developing predictive models in clinical psychiatry data to classify diseases, predict treatment outcomes or improve treatment selections. In particular, these data-driven approaches are built upon several machine learning techniques whose predictive models have been pre-processed, trained, optimised, post-processed and tested in novel computationally intensive frameworks. In the second phase, this document advances research in medical data mining by proposing several novel extensions in the area of data classification by offering a novel decision tree algorithm, which we call PIDT, based on parameterised impurities and statistical pruning approaches toward building more accurate decision trees classifiers and developing new ensemblebased classification methods. In particular, the experimental results show that by building predictive models with the novel PIDT algorithm, these models primarily led to better performance regarding accuracy and tree size than those built with traditional decision trees. The contributions of the proposed dissertation can be summarised as follow. Firstly, several statistical and machine learning algorithms, plus techniques to improve these algorithms, are explored. Secondly, prediction modelling and pattern detection approaches for the first-episode psychosis associated with cannabis use are developed. Thirdly, a new computationally intensive machine learning framework for understanding the link between cannabis use and first-episode psychosis was introduced. Then, complementary and equally sophisticated prediction models for the first-episode psychosis associated with cannabis use were developed using artificial neural networks and deep learning within the proposed novel computationally intensive framework. Lastly, an efficient novel decision tree algorithm (PIDT) based on novel parameterised impurities and statistical pruning approaches is proposed and tested with several medical datasets. These contributions can be used to guide future theory, experiment, and treatment development in medical data mining, especially psychiatry.

Treatment of people at ultra-high risk for psychosis.

Does tobacco use cause psychosis? Systematic review and meta-analysis

Therapy initiation during a first acute episode psychosis in the psychiatric department of Mahdia

BackgroundIndividuals with attenuated or sub-threshold psychotic symptoms (STPS) are considered at-risk for psychosis. The notion that STPS represent “early psychosis” holds promise as it suggests the possibility of charting the developmental course of psychotic illness with neuroimaging. However, recent evidence suggests that a significant minority of patients in a first episode of psychosis (FEP) do not recall pre-onset STPS, suggesting diversity in early positive symptom course. This diversity may be reflected at the level of neurodevelopment. While imaging studies of at-risk youth and FEP patients reveal progressive trends in cortical thinning across stages of illness, none have considered the STPS history of FEP patients. To better understand neurobiological trends across illness stages, we investigate the relationships between STPS history and cortical thickness in FEP patients using a whole-brain approach.MethodsPatients (N=93) were recruited from a specialized early intervention clinic for FEP at the Douglas Mental Health University Institute. The Circumstances of Onset and Relapse Schedule was administered to identify youth who recalled at least one of nine expert-selected STPS prior to their FEP (STPS+, N=67) compared to those who did not (STPS-, N=26). These STPS include: Suspiciousness or odd ideas of reference, odd or bizarre ideas that are not delusional, unusual or eccentric behavior, unusual perceptual experiences that are not clearly psychotic, disorganized or odd speech, inappropriate affect, hallucinations or delusions (sub-threshold), and passivity experiences. Age and sex-matched healthy controls were recruited (N=83) for comparison. Participants were scanned on a 1.5T MRI scanner between 1 and 3 times at baseline, at 1-year follow-up, and at 2-year follow-up. Structural T1-weighted images were processed through the CIVET 2.1 pipeline. Cortical thickness values of 320 scans (143 HC, 123 STPS+, 54 STPS-) that passed quality control were extracted for group analysis. Linear mixed effects models controlling for effects of age, sex, education, and mean whole-brain thickness were applied to obtain vertex-wise F-test maps comparing groups.ResultsPost-hoc vertex-wise t-test maps were thresholded with Random Field Theory (p-cluster=0.001) and revealed that compared to controls, only STPS- patients exhibited significantly thinner cortical thickness in the right inferior frontal gyrus (peak t(162.3)=4.13, p<0.001). Examination of mean cortical thickness within this cluster, comparing patient groups only, revealed that compared to STPS+ patients, STPS- patients exhibited significantly thinner cortical thickness (t(172)=-2.55, p=0.01). This difference was most pronounced at baseline.DiscussionThese results indicate that within the right prefrontal cortex, STPS+/- patients may undergo different cortical maturation trajectories leading up to and through a first episode of psychosis. These differences may explain differential vulnerability to sub-threshold psychotic symptomology before a full-blown episode. In addition to suggesting differential underlying neurobiology related to STPS, these results suggest the importance of considering STPS history in mapping the trajectories of cortical thickness among FEP patients.

Approximately one-third of patients presenting with a first episode of psychosis have a history of cannabis use. Some of these patients meet the criteria for cannabis-induced psychotic disorder (CIPD), which is regarded as a disorder with better outcomes compared to other psychotic disorders. The aim of this paper was to determine whether there are differences in clinical and demographic features between patients with CIPD and patients with a first episode of primary psychotic disorder (PPD) with concurrent cannabis use (CU). A literature search in the PubMed database for papers published in English was conducted. A total of 12 studies published between 2002 and 2019 were selected. Available data support the hypothesis that CIPD is a distinct clinical entity from PPD with CU. Differences were found in clinical presentation, as patients with CIPD tend to have a lower intensity of overall psychotic symptoms, greater insight into psychosis, a higher likelihood of visual hallucinations, depersonalization, and derealization, as well as more intense manic symptoms and hostility than patients with PPD with CU. In terms of family history, patients with CIPD are more likely to have a close relative with a substance use disorder but less likely to have a close relative diagnosed with a psychotic disorder. However, a significant percentage (25-45%) of patients initially treated for CIPD will meet criteria for a chronic psychotic disorder in the following years, and continuous cannabis use is associated with poor prognosis, independent of the initial diagnosis. In these conditions, early intervention is crucial, and substance use treatment should be considered a priority for cannabis users who develop psychotic symptoms.

Objective: The comorbidity of substance use disorders (SUD) in psychotic disorders are common. In this study, it was aimed to investigate whether there was any difference in treatment choice, duration and treatment benefit in adolescents with first episode psychosis (FEP) diagnosis in the presence of SUD comorbidity. Methods: The study included 56 people aged between 14-18 years who were diagnosed with IAP and hospitalized. The sociodemog-raphic data form was completed by interviewing all the patients and their families. Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression Scale (CGI) and Young Mania Rating Scale were used. After the interview, patients were divided into two groups, one at the lifetime and/or cur-rently being diagnosed with SUD (26 patients) and not (30 patients). Results: In the SUD comorbid group the most frequent used substances were determined as synthetic cannabinoids (46.2%) and cannabis (23.1%). Olanzapine, biperiden and benzodiazepines were more common used in the IAP group, and risperidone was more preferred in the comorbid group. The duration of hospitalization were similar. When the scale scores in the entry and discharge were compared, higher scores were found in the PANNS positive subscale scores in the comorbid group. There was no difference between the two groups when the improvement rates between the entry and discharge scale scores were compared. Conclusion: Studies on the frequency of psychoactive substances use in psychotic disor-ders are common, but our data on the effect of its on the treatment process are quite limited, especially during adolescent age. In our study, in the presence of SUD comorbidity although there are no differences in the duration of treatment and benefit from the treatment, larger samples and follow-up studies are needed.

Gender differences in premorbid, entry, treatment, and outcome characteristics in a treated epidemiological sample of 661 patients with first episode psychosis

Abrupt cessation of heavy cannabis use can cause a withdrawal syndrome characterised by irritability, anxiety, insomnia, reduced appetite and restlessness. Recent reports have also described people in whom cannabis withdrawal immediately preceded the acute onset of psychosis. To identify cases of psychosis associated with cannabis withdrawal. We completed a systematic review of the literature, which comprised case reports, case series and other studies. We also searched a large electronic database of psychiatric healthcare records. The systematic review identified 44 individuals from 21 studies in whom cannabis withdrawal preceded the development of acute psychosis. In the health record study, we identified another 68 people, of whom 47 involved a first episode of psychosis and 21 represented further episodes of an existing psychotic disorder. Almost all people were daily cannabis users who had stopped using cannabis abruptly. Individuals who continued to use cannabis after the acute psychotic episode had a much higher risk of subsequent relapse than those who abstained (odds ratio 13.9 [95% CI: 4.1 to 56.9]; χ2 = 20.1, P < 0.00001). Abrupt cannabis withdrawal may act as a trigger for the first episode of psychosis and a relapse of an existing psychosis. Acute psychotic symptoms can emerge after the cessation, as well as following the use, of cannabis.

Psychotic disorders are heterogeneous disorders for which there is evidence of structural and functional brain abnormalities. The role of white matter integrity, often measured via Fractional Anisotropy (FA), has played a controversial role in individuals with a first episode of psychosis (FEP). Similarly, some FEP studies have observed that higher FA is associated with better verbal memory, but others failed to find such an association. Studying the early stages of psychosis represents a promising avenue to overcome previous confounding factors and characterize the disease in its early clinical stages. Eighty individuals with a FEP were recruited from a specialized early intervention program for psychosis alongside 55 non-clinical controls from the community matched for age and sex. Both groups were followed and scanned 4 times: at baseline (within 3months after program entry), 6months, 12months, and 18months. Tract-Based Spatial Statistics (TBSS) were used on 3.0 Tesla diffusion-weighted images to extract fractional anisotropy values for white matter regions of interest in accordance with the John Hopkins University white-matter tractography atlas. The analysis revealed no significant main effect of group or time, and no significant associations between FA and verbal memory. Overall, differences in FA are small early in the course of illness and longer follow-up periods may be required to identify possible changes during a critical intervention window.

Objectives: Although pharmacotherapy with antipsychotic medication is an effective intervention for early psychosis (EP), drop out from treatment and relapse rates appear still relatively high. In the last decade, there is growing interest in Cognitive-Behavioural Therapy (CBT) as early intervention for EP. Some studies suggest that CBT may be an effective adjuvant to pharmacotherapy to reduce risk of development of chronic psychosis in individuals who experienced first episodes. Symptoms of depression and social anxiety are very common among patients experiencing first episode psychosis, thus impairing quality of life and functioning. This aspect may create a negative vicious cycle, that may reinforce feelings of learned helplessness and hopelessness with regard to psychosis diagnosis, thus increasing vulnerability to relapse in further episodes. However, there is little knowledge on the use of CBT to target both reoccurrence of psychotic episodes and symptoms of depression and social anxiety secondary to first psychotic episodes. The current case report presents the administration of a modular CBT semi-manualized intervention to a young patient to enhance prevention of psychosis and target symptoms of social anxiety and depression following first psychotic episodes. Methods: Treatment consisted in 21 individual weekly sessions, delivered in an outpatient setting, involving two phases. The first one targeted prevention of psychotic episodes. Case formulation was developed according to cognitive behavioural model of psychosis. Psychoeducation on early signs and vulnerability factors of relapse in psychotic episodes was delivered in order to promote patient’s self-monitoring and insight on positive symptoms prodromes. The second treatment phase targeted symptoms of depression and social anxiety. Homework based on behavioural activation were assigned in order to address depressive symptoms, and cognitive restructuring was used to normalize dysfunctional beliefs. A social skills and assertiveness training was used to target social anxiety. CBT treatment was delivered in combination with medication. Clinical interviews were conducted at pre-, immediate post-treatment, and at 5-month-follow-up, to evaluate reoccurrence of psychotic episodes, and changes in depression, social anxiety, and functioning. Results: As observed by clinical interviews, the patient did not experience further relapse in psychotic episodes. In addition, it was observed a reduction in depressive symptoms and social anxiety through the increase of the number of daily activities, social relations, work and academic engagement. Conclusions: Important limitations of the study are discussed. Future research using large randomized controlled trials with longer follow-up assessments should evaluate the effectiveness of CBT to target depressive symptoms and social anxiety for patients with EP.

Investigating the relationship between premorbid and prodromal status and the clinical manifestations of the first psychotic episode is relevant for understanding the pathophysiology of psychosis and for improving management of the disease. This study examined patterns of premorbid functioning of persons interviewed during their first episode of psychotic illness and examined the relationship of premorbid characteristics with symptom severity and cognitive functioning during the first illness episode. The data were derived from the baseline assessments of a multicenter international drug trial that enrolled 535 patients in their first episode of psychosis. Subjects' scores on the Premorbid Adjustment Scale were used to assign them to groups according to whether their premorbid functioning was stable-good, stable-poor, or deteriorating. The three groups' scores on the Positive and Negative Syndrome Scale, Clinical Global Impression (CGI) severity scale, and a cognitive battery were compared. Almost half of the patients (47.5%) had stable-good premorbid functioning, 37.3% had stable-poor premorbid functioning, and 15.1% had initially good, but later deteriorating, premorbid functioning. Compared to the stable-poor and deteriorating groups, the stable-good group had lower (better) negative syndrome and general psychopathology scores on the Positive and Negative Syndrome Scale and a lower CGI severity scale score. Differences between the stable-poor and stable-good groups were also found on some cognitive measures and on the positive syndrome subscale of the Positive and Negative Syndrome Scale. More than half of the subjects, who were interviewed during their first episode of psychotic disorder, had evident premorbid behavioral disturbances. Poor premorbid functioning before onset of psychosis was associated with more severe symptoms and more severe cognitive manifestations of illness during the first illness episode.