Brain connectomes in youth at risk for serious mental illness: an exploratory analysis.

BACKGROUND: Identifying early biomarkers of serious mental illness (SMI)-such as changes in brain structure and function-can aid in early diagnosis and treatment. Whole brain structural and functional connectomes were investigated in youth at risk for SMI. METHODS: Participants were classified as healthy controls (HC; n = 33), familial risk for serious mental illness (stage 0; n = 31), mild symptoms (stage 1a; n = 37), attenuated syndromes (stage 1b; n = 61), or discrete disorder (transition; n = 9) based on clinical assessments. Imaging data was collected from two sites. Graph-theory based analysis was performed on the connectivity matrix constructed from whole-brain white matter fibers derived from constrained spherical deconvolution of the diffusion tensor imaging (DTI) scans, and from the correlations between brain regions measured with resting state functional magnetic resonance imaging (fMRI) data. RESULTS: Linear mixed effects analysis and analysis of covariance revealed no significant differences between groups in global or nodal metrics after correction for multiple comparisons. A follow up machine learning analysis broadly supported the findings. Several non-overlapping frontal and temporal network differences were identified in the structural and functional connectomes before corrections. CONCLUSIONS: Results suggest significant brain connectome changes in youth at transdiagnostic risk may not be evident before illness onset.

Diffusion kurtosis imaging of white matter in bipolar disorder.

White matter pathology likely contributes to the pathogenesis of bipolar disorder (BD). Most studies of white matter in BD have used diffusion tensor imaging (DTI), but the advent of more advanced multi-shell diffusion MRI imaging offers the possibility to investigate other aspects of white matter microstructure. Diffusion kurtosis imaging (DKI) extends the DTI model and provides additional measures related to diffusion restriction. Here, we investigated white matter in BD by applying whole-brain voxel-based analysis (VBA) and a network-based connectivity approach using constrained spherical deconvolution tractography to assess differences in DKI and DTI metrics between BD (n = 25) and controls (n = 24). The VBA showed lower mean kurtosis in the corona radiata and posterior association fibers in BD. Regional differences in connectivity were indicated by lower mean kurtosis and kurtosis anisotropy in streamlines traversing the temporal and occipital lobes, and lower mean axial kurtosis in the right cerebellar, thalamo-subcortical pathways in BD. Significant differences were not seen in DTI metrics following FDR-correction. The DKI findings indicate altered connectivity across cortical, subcortical and cerebellar areas in BD. DKI is sensitive to different microstructural properties and is a useful complementary technique to DTI to more fully investigate white matter in BD.

White matter microstructure in youth at risk for serious mental illness: A comparative analysis.

Identifying biomarkers of serious mental illness, such as altered white matter microstructure, can aid in early diagnosis and treatment. White matter microstructure was assessed using constrained spherical deconvolution of diffusion imaging data in a sample of 219 youth (age 12-25 years, 64.84% female) across 8 sites. Participants were classified as healthy controls (HC; n = 47), familial risk for serious mental illness (n = 31), mild-symptoms (n = 37), attenuated syndromes (n = 66), or discrete disorder (n = 38) based on clinical assessments. Fractional anisotropy (FA) and mean diffusivity (MD) values were derived for the whole brain white matter, forceps minor, anterior cingulate, anterior thalamic radiations (ATR), inferior fronto-occipital fasciculus, superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF). Linear mixed effects models showed a significant effect of age on MD of the left ATR, left SLF, and left UF, and a significant effect of group on FA for all tracts examined. For most tracts, the discrete disorder group had significantly lower FA than other groups, and the attenuated syndromes group had higher FA compared to HC, with few differences between the remaining groups. White matter differences in MDD are most evident in individuals following illness onset, as few significant differences were observed in the risk phase.

Substance use in youth at-risk for serious mental illness.

AIM: The aim of this paper is to describe the substance use of participants who are at-risk for serious mental illness (SMI). METHOD: The Canadian Psychiatric Risk and Outcome study (PROCAN) is a two-site study of 243 youth and young adults aged 13 to 25 years, categorized into four groups: healthy controls (n = 42), stage 0 (asymptomatic individuals with risk of SMI typically family high risk; n = 41), stage 1a (distress disorder or mild symptoms of anxiety or depression; n = 53) and stage 1b (attenuated syndromes, including bipolar disorder or psychosis; n = 107). Substance use measures were administered at baseline, 6- and 12-months. RESULTS: At baseline, the most commonly reported substance used in the past month was alcohol (43.6%), followed by cannabis (14.4%) and tobacco (12.4%). There were no significant group differences in use. 42.4% of all participants reported ever using cannabis in their lifetime, whereas 21.4% reported currently using cannabis. There were no group differences in ever having used cannabis. Regarding lifetime substance abuse disorders, cannabis use disorder (5.7%) and alcohol use disorder (4.5%) were the most common and more often reported in stage 1b participants relative to other groups. Furthermore, alcohol, cannabis and tobacco use remained relatively consistent at 6- and 12-month follow-ups when compared to baseline use. CONCLUSION: Alcohol was the most commonly used substance followed by cannabis and tobacco. Although substance use did not differ between those at different stages of risk, overall prevention strategies are still warranted for youth at-risk for SMI, especially those who are more symptomatic and potentially at greater risk of developing an SMI.

A Family Study of Trauma and Coping Strategies in Gambling Disorder.

Family studies can provide a wealth of information regarding risk factors in psychological disorders. No studies have compared the trauma experiences and coping strategies of problem gamblers with those of their first-degree relatives. Therefore, in this study, childhood trauma and coping strategies were investigated among participants with gambling disorder, their first-degree biological relatives, and community controls. Participants completed diagnostic interviews and symptom severity assessments. Participants also completed the Childhood Trauma Questionnaire (CTQ) which assesses history of abuse and neglect, and the Coping Inventory for Stressful Situations (CISS) which assesses task, emotion, and avoidance oriented coping strategies. Analysis of variance showed that there was a significant effect for group, but not gender, on the CTQ. Multivariate analysis of variance revealed a significant effect for group on coping style. Post-hoc tests showed that probands and relatives were less likely to use task-oriented coping compared to controls, but probands and relatives did not differ from each other on task-oriented coping. Mediation analysis showed that task-oriented coping did not mediate the relation between childhood trauma and gambling severity. By using a family study design, this study was able for the first time to delineate familial and disease-specific effects associated with childhood trauma and coping strategies in gambling disorder.

White Matter Connectivity in Youth at Risk for Serious Mental Illness: A Longitudinal Analysis.

Longitudinal changes in white matter connectivity were assessed in a sample of youth at-risk for serious mental illness (n=183; age 12-25). Diffusion tensor imaging (DTI) was acquired at baseline and 12 months from youth recruited across two sites and classified as healthy controls (n=36), familial risk (n=30), mild-symptoms (n=41), attenuated syndromes (n=70), or transition (n=9) based on clinical assessments. Fractional anisotropy (FA) and mean diffusivity (MD) values were derived for the whole brain white matter, forceps minor, anterior cingulate, anterior thalamic radiations, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. MANCOVA analysis controlling for site, sex, and age showed no significant group differences in FA and MD at baseline or at 12 months. Linear mixed effects analysis showed a significant effect for time for most white matter tracts, but no effect for group, or group by time interaction. Transdiagnostic risk groups have similar profiles of WM connectivity and similar rates of change over time.

Cannabis use in individuals at clinical high-risk for psychosis: a comprehensive review.

PURPOSE: The objectives of this review were to understand the prevalence of cannabis use and how cannabis is associated with transition to psychosis, symptoms, cognition, trauma and family history in clinical high risk (CHR) for psychosis individuals. METHOD: A systematic literature review was conducted to find studies that examined cannabis use in CHR individuals, with no limitations on the geographical area, and included publications up to November 2018. Studies were screened for inclusion based on detailed criteria, and data were extracted on cannabis use and associated outcomes. A quantitative synthesis by meta-analysis was performed where appropriate, otherwise, a qualitative synthesis was conducted. RESULTS: Overall, 36 studies met inclusion criteria with an average age of 20.1 years and 58.4% males. Prevalence of lifetime cannabis use was 48.7%, whereas current cannabis use was 25.8% and the prevalence of cannabis use disorder/abuse or dependence was 14.9% across the studies. All cannabis use results had statistically significant heterogeneity ranging from 75.7 to 92.8%. The most commonly reported association with cannabis use was transition to psychosis, although the pooled relative risk (RR) was not statistically significant (RR = 1.11, 95% confidence interval = 0.89-1.37). For all other outcomes including symptoms, cognition, trauma, and family history, the evidence was limited, and therefore, the results were synthesized qualitatively. CONCLUSION: Almost half of CHR individuals have ever used cannabis. However, cannabis use has not been thoroughly researched regarding frequency and dose of use, and how other factors, such as symptoms, are associated with cannabis in CHR individuals.

A Comparison of Self-Reported Impulsivity in Gambling Disorder and Bipolar Disorder.

The present study investigated self-reported impulsivity in gambling disorder (GD) and bipolar disorder (BD). Participants with GD (n = 31), BD (n = 19), and community controls (n = 68) completed diagnostic interviews and symptom severity and functioning assessments. Participants also completed the UPPS-P Impulsive Behavior Scale composed of five dimensions including urgency (i.e., acting rashly under conditions of negative or positive emotion), lack of perseverance (i.e., inability to maintain focus), lack of premeditation (i.e., inability to consider negative consequences), and sensation seeking (i.e., tendency to pursue novel and exciting activities). Multivariate analysis of variance showed overall significant differences among the diagnostic groups on the UPPS-P subscales. Follow-up analyses of variance showed that the groups differed on all subscales except sensation seeking. The gambling and bipolar groups had significantly higher levels of self-reported impulsivity on all subscales when compared to controls. In addition, the BD group showed higher levels of positive urgency when compared to the GD group. Positive and negative urgency showed the strongest association with GD and BD. Impaired emotion regulation mechanisms may underlie self-reported impulsivity in both disorders. Lack of premeditation and perseverance may be related to dysfunctional cognitive processes.

Schizophrenia, narrative, and neurocognition: The utility of life-stories in understanding social problem-solving skills.

OBJECTIVE: Schizophrenia researchers have focused on phenomenological aspects of the disorder to better understand its underlying nature. In particular, development of personal narratives-that is, the complexity with which people form, organize, and articulate their "life stories"-has recently been investigated in individuals with schizophrenia. However, less is known about how aspects of narrative relate to indicators of neurocognitive and social functioning. The objective of the present study was to investigate the association of linguistic complexity of life-story narratives to measures of cognitive and social problem-solving abilities among people with schizophrenia. METHOD: Thirty-two individuals with a diagnosis of schizophrenia completed a research battery consisting of clinical interviews, a life-story narrative, neurocognitive testing, and a measure assessing multiple aspects of social problem solving. Narrative interviews were assessed for linguistic complexity using computerized technology. RESULTS: The results indicate differential relationships of linguistic complexity and neurocognition to domains of social problem-solving skills. More specifically, although neurocognition predicted how well one could both describe and enact a solution to a social problem, linguistic complexity alone was associated with accurately recognizing that a social problem had occurred. In addition, linguistic complexity appears to be a cognitive factor that is discernible from other broader measures of neurocognition. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Linguistic complexity may be more relevant in understanding earlier steps of the social problem-solving process than more traditional, broad measures of cognition, and thus is relevant in conceptualizing treatment targets. These findings also support the relevance of developing narrative-focused psychotherapies. (PsycINFO Database Record

Measuring Fluid Intelligence in Healthy Older Adults.

The present study evaluated subjective and objective cognitive measures as predictors of fluid intelligence in healthy older adults. We hypothesized that objective cognitive measures would predict fluid intelligence to a greater degree than self-reported cognitive functioning. Ninety-three healthy older (>65 years old) community-dwelling adults participated. Raven's Advanced Progressive Matrices (RAPM) were used to measure fluid intelligence, Digit Span Sequencing (DSS) was used to measure working memory, Trail Making Test (TMT) was used to measure cognitive flexibility, Design Fluency Test (DFT) was used to measure creativity, and Tower Test (TT) was used to measure planning. The Cognitive Failures Questionnaire (CFQ) was used to measure subjective perceptions of cognitive functioning. RAPM was correlated with DSS, TT, and DFT. When CFQ was the only predictor, the regression model predicting fluid intelligence was not significant. When DSS, TMT, DFT, and TT were included in the model, there was a significant change in the model and the final model was also significant, with DFT as the only significant predictor. The model accounted for approximately 20% of the variability in fluid intelligence. Our findings suggest that the most reliable means of assessing fluid intelligence is to assess it directly.

Analyzing Confabulations in Schizophrenia and Healthy Participants.

OBJECTIVES: Confabulations occur in schizophrenia and certain severe neuropsychiatric conditions, and to a lesser degree in healthy individuals. The present study used a forced confabulation paradigm to assess differences in confabulation between schizophrenia patients and healthy controls. METHODS: Schizophrenia patients (n=60) and healthy control participants (n=19) were shown a video with missing segments, asked to fill in the gaps with speculations, and tested on their memory for the story. Cognitive functions and severity of symptoms were also evaluated. RESULTS: Schizophrenia patients generated significantly more confabulations than healthy control participants and had a greater tendency to generate confabulations that were related to each other. Schizophrenic confabulations were positively associated with temporal context confusions and formal thought disorder, and negatively with delusions. CONCLUSIONS: Our findings show that the schizophrenia patients generate more confabulations than healthy controls and schizophrenic confabulations are associated with positive symptoms. (JINS, 2016, 22, 911-919).

Idea density in the life-stories of people with schizophrenia: Associations with narrative qualities and psychiatric symptoms.

Disordered speech and language deficits are well-documented in schizophrenia-spectrum disorders. Researchers often assess speech samples using manualized rating systems, though recently computerized language assessment methods have been used more frequently in the study of speech from people with schizophrenia. Most typically, these computerized assessments measure aspects of expressivity (i.e., pause durations, prosody) or use word-count technology; less attention has focused on similar methods that can capture more sophisticated aspects of linguistic complexity (e.g., idea density). The primary objective of the present study was to assess idea density - via a computerized measure - in the life-story narratives of people with schizophrenia (n=32) compared to a group of community control participants (n=15). In the schizophrenia group, we also examined associations between idea density, narrative qualities rated via a manualized measure, and psychiatric symptoms. Our findings indicate that idea density is diminished in individuals with schizophrenia compared to controls. Further, our results suggest that though people with schizophrenia with richer idea density tended to have more developed insight into illness, they also had higher levels of depression, anxiety, and avolition. Implications of these results and suggestions for future research are discussed.

Confabulations in schizophrenia.

INTRODUCTION: Current theories of confabulation are based primarily on the observation of neurological patients. The present paper evaluates these theories based on evidence from schizophrenia. Schizophrenia is unique in that it presents with a pathophysiology which differs from that of other neuropsychiatric conditions, and yet the candidate's deficits that various theories of confabulation implicate are often simultaneously present in schizophrenia. METHODS: A selective review of literature on schizophrenic and neurological confabulations was undertaken. RESULTS: Schizophrenic confabulation differs from neurological confabulation in terms of its characteristic features and association with symptoms, cognition and linguistic functions. Current evidence also suggests that confabulation may be conceptualized as a special class of delusions pertaining to memory phenomena. CONCLUSIONS: Schizophrenia presents with confabulations that cannot be fully accounted for by the existing theories. It also presents with confabulations with unique features, which have different cognitive correlates and relation to other symptoms of the condition.

Internal versus external auditory hallucinations in schizophrenia: symptom and course correlates.

INTRODUCTION: The auditory hallucinations associated with schizophrenia are phenomenologically diverse. "External" hallucinations classically have been considered to reflect more severe psychopathology than "internal" hallucinations, but empirical support has been equivocal. METHODS: We examined associations of "internal" versus "external" hallucinations with (1) other characteristics of the hallucinations, (2) severity of other symptoms and (3) course of illness variables, in a sample of 97 stable outpatients with schizophrenia or schizoaffective disorder who experienced auditory hallucinations. RESULTS: Patients with internal hallucinations did not differ from those with external hallucinations on severity of other symptoms. However, they reported their hallucinations to be more emotionally negative, distressing and long-lasting, less controllable and less likely to remit over time. They also were more likely to experience voices commenting, conversing or commanding. However, they also were more likely to have insight into the self-generated nature of their voices. Patients with internal hallucinations were not older, but had a later age of illness onset. CONCLUSIONS: Differences in characteristics of auditory hallucinations are associated with differences in other characteristics of the disorder, and hence may be relevant to identifying subgroups of patients that are more homogeneous with respect to their underlying disease processes.

Utility of a computerized, paced semantic verbal fluency paradigm in differentiating schizophrenia and healthy subjects.

Functional magnetic resonance imaging (fMRI) paradigms designed to study word generation traditionally utilize a computerized paced version of the verbal fluency task (VFT) comprising 'blocks' of word generation and a baseline word repetition task. The utility of the above paced VFT paradigm in differentiating neuropsychiatric patients from healthy subjects has not been systematically examined. We administered a computerized, paced version of the semantic VFT comprising word generation and word repetition blocks to 24 schizophrenia and 24 matched healthy subjects, both before and during fMRI acquisition. The performance of patients with schizophrenia was significantly inferior to that of healthy control subjects in both the 'pre-scan' and 'intra-scan' sessions of the computerized paced semantic VFT. Specifically, schizophrenia patients generated significantly fewer total responses (VFTR) as well as correct responses (VFCR), but a larger number of 'no response' trials. However, there were no significant group differences in perseverative responses in the pre-scan session or 'intra-scan' sessions. The above computerized task has been reported by us previously to generate a behavioral performance index with hemodynamic correlates (John et al., 2011). Thus, our findings support the use of computerized paced VFT comprising word generation and word repetition blocks in both clinical and research settings.

Effects of social cognitive impairment on speech disorder in schizophrenia.

Disordered speech in schizophrenia impairs social functioning because it impedes communication with others. Treatment approaches targeting this symptom have been limited by an incomplete understanding of its causes. This study examined the process underpinnings of speech disorder, assessed in terms of communication failure. Contributions of impairments in 2 social cognitive abilities, emotion perception and theory of mind (ToM), to speech disorder were assessed in 63 patients with schizophrenia or schizoaffective disorder and 21 nonpsychiatric participants, after controlling for the effects of verbal intelligence and impairments in basic language-related neurocognitive abilities. After removal of the effects of the neurocognitive variables, impairments in emotion perception and ToM each explained additional variance in speech disorder in the patients but not the controls. The neurocognitive and social cognitive variables, taken together, explained 51% of the variance in speech disorder in the patients. Schizophrenic disordered speech may be less a concomitant of "positive" psychotic process than of illness-related limitations in neurocognitive and social cognitive functioning.

Pesticides and breast cancer risk: a comparison between developed and developing countries.

BACKGROUND: A large number of studies in Europe and US find little or no association between pesticides and breast cancer, adding to the increasingly dominant view that pesticides are not causally related to breast cancer. We investigated whether there are any differences in the levels of pesticides like dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB), hexachlorobenzene (HCB) and hexachlorocyclohexane (HCH) and their effect for the development of breast cancer between developed and developing countries. METHODS: A pubmed search for literature on pesticides, organochlorines, organophosphates and breast cancer risk from 1990 through 2009 was carried out. RESULTS: The level of pesticide exposure is higher in developing world than the developed world. DDT is found to be positively associated with breast cancer risk. Results for other pesticides are equivocal. There is a dearth of studies in developing countries, which cannot be made up for generalizing the results from developed countries to the developing and third world. CONCLUSIONS: More studies are needed in the developing and third world countries, investigating the relation between pesticides and breast cancer risk as the sheer amount of pesticides being relentlessly used in these countries due to lack of proper government regulations.