Structural connectivity between the hippocampus and cortical/subcortical area relates to cognitive impairment in schizophrenia but not in mood disorders

Cognitive impairment in schizophrenia and other psychiatric disorders is a challenge to be overcome in order to maintain patients' quality of life and social function. The neurological pathogenesis of cognitive impairment requires further elucidation. In general, the hippocampus interacts between the cortical and subcortical areas for information processing and consolidation and has an important role in memory. We examined the relationship between structural connectivity of the hippocampus and cortical/subcortical areas and cognitive impairment in schizophrenia, major depressive disorder and bipolar disorder. Subjects comprised 21 healthy controls, 19 patients with schizophrenia, 20 patients with bipolar disorder and 18 patients with major depressive disorder. Diffusion-weighted tensor images data were processed using ProbtrackX2 to calculate the structural connectivity between the hippocampus and cortical/subcortical areas. Cognitive function was assessed using the Brief Assessment of Cognition in schizophrenia composite score. Hippocampal structural connectivity index was significantly correlated with composite score in the schizophrenia group but not in the healthy control, major depressive disorder or bipolar disorder groups. There were no statistically significant differences in hippocampal structural connectivity index between the four groups. Structural connectivity between the hippocampus and cortical/subcortical areas is suggested to be a pathophysiological mechanism of comprehensive cognitive impairment in schizophrenia.     

Creative Cognition and Psychosis Vulnerability: What’s the Difference?

Evidence from experimental psychology provides unequivocal support for enhanced creativity among individuals who are prone to psychotic and mood disorders. At the same time, there is strong epidemiological evidence for greater incidence of creative achievement among those diagnosed with bipolar disorder (but not schizophrenia). This review examines the evidence for common factors predisposing an individual to creativity and psychosis, as well as factors that distinguish the capacity for creative achievement from the creative potential that may be inherent in psychosis vulnerability. Factors implicated as common to creative potential and psychosis vulnerability include enhanced divergent thinking, reduced latent inhibition and preattentive filtering mechanisms; on the other hand, greater cognitive flexibility, motivation, and openness to experience tend to be associated with creative achievement, but not psychosis. This evidence is considered with respect to the utility of tailored vocational interventions to effectively harness creative potential, which may be useful for young individuals in the early stages of illness or their unaffected family members.     

Patient preferences for medicine administration for acute agitation: results from an internet-based survey of patients diagnosed with bipolar disorder or schizophrenia in two Nordic countries

The objective was to elicit patient preferences for medicine administration method in the management of acute agitation episodes among patients diagnosed with bipolar disorder or schizophrenia. The patients’ experiences of acute agitation episodes and their management of episodes were also explored. Data were collected via an anonymous, internet-based survey of residents in Denmark or Sweden with schizophrenia or bipolar disorder (October 2014 to December 2014). Inclusion criteria were having a diagnosis of schizophrenia or bipolar disorder, and being above 18 years of age. The questionnaire included questions about preferences for medication attributes, experiences with pharmacological treatment for agitation and involvement in treatment plans. A total of 237 diagnosed patients (61 with schizophrenia; 176 with bipolar disorder) completed the questionnaire. Agitation episodes were experienced by 90% of the respondents. In total, 83% of the respondents reported having received treatment with tablets. When patients were presented with the attributes of an inhalation method, respondents stated that the fast onset of action, low risk of adverse reactions and least invasive form of drug delivery were positive attributes of treatment with inhalation. Inhalation is a new delivery route for treatment of acute agitation in patients diagnosed with bipolar disorder or schizophrenia. Inhalation is the preferred treatment method for acute agitation among Danish and Swedish patients with bipolar disorder or schizophrenia.     

Schizophrenia: A Neurodevelopmental Perspective

Diverse lines of research suggest that schizophrenia is a genetically influenced neurodevelopmental disorder. Family, twin, and adoption studies suggest that most cases of schizophrenia involve a genetic diathesis that is necessary but not sufficient for development of the disorder. Histological, neuroimaging, and neuropsychological findings converge in providing evidence for medial-temporal and frontal lobe dysfunction that likely predates the onset of psychosis. Behavioral phenomenology and neurobiology suggest that dopamine plays a crucial moderating role between these structural abnormalities and functional impairment. Recently, investigators have used animal models and clinical syndromes to integrate these findings into neurodevelopmental models of schizophrenia that hold great potential for yielding etiological insight.     

Suicidal behavior in schizophrenia and schizoaffective disorder: examining the role of depression

Understanding the relationship between depression and suicidal behavior among individuals with schizophrenia and schizoaffective disorder can aid assessment and treatment. In this study, 86 individuals with schizophrenia and schizoaffective disorder were assessed for past and current suicidal behavior, depression, hopelessness, and reasons for living. Thirty-four percent reported a history of suicide attempts. Suicidal behavior typically occurred 4.5 years after the onset of psychosis and 7.5 years after the onset of the first major depressive episode for those who had a history of major depression. Depression was frequent among both attempters and non-attempters, but only half of the attempters reported a suicide attempt during an episode of major depression. And almost half of those with depression never made a suicide attempt despite a long history of illness. Although depression is a potential stressor for triggering suicidal behavior in a vulnerable subset of individuals with schizophrenia, schizophrenia research must identify other risk factors for suicidal behavior. Clinicians should remember that even without a depressive episode there is still a significant risk for suicidal behavior in schizophrenia.     

A Systematic Review of Studies Reporting Data-Driven Cognitive Subtypes across the Psychosis Spectrum

Neuropsychology Review - The delineation of cognitive subtypes of schizophrenia and bipolar disorder may offer a means of determining shared genetic markers and neuropathology among individuals...     

Suicidal behavior among inpatients with schizophrenia and mood disorders in Chengdu, China

This study evaluated the characteristics of suicidal behavior (suicide attempt or suicidal ideation) among 230 consecutively admitted inpatients with schizophrenia and mood disorders in a university hospital in China. The rate of lifetime suicidal behavior was found to be significantly higher in patients with mood disorders (62.4%) than in patients with schizophrenia (38.6%). The rate of suicidal behavior was significantly higher in patients with major depressive disorder (86.8%) than those with bipolar disorders (42.6%). Patients with schizophrenia attempted suicide for the first time earlier in life than the patients with mood disorders. Mood disorder patients, especially those with major depressive disorder, had more and more serious suicide attempts than the patients with schizophrenia.     

Distinguishing bipolar depression, major depression, and schizophrenia with the MMPI-2 clinical and content scales

Clinical and content scales from the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) were used to examine the capacity of these scales to assist in the differential diagnosis of a sample of 212 psychiatric patients-137 with major depression; 43 with schizophrenia; and 32 with bipolar disorder, depressed state. Consistent with the previous literature, the clinical scales Depression (D), and Schizophrenia (Sc), and the content scales Depression (DEP), and Low Self-Esteem (LSE) best distinguished major depression from schizophrenia; the content scale DEP proved to be the most powerful predictor in distinguishing bipolar depression from schizophrenia. No clinical or content scale proved to be effective in distinguishing patients with bipolar depression from patients with major depression. In general, the content scales outperformed the clinical scales.     

Smooth-pursuit eye tracking in first-episode psychotic patients and their relatives.

We wished to determine the specificity of smooth-pursuit eye tracking dysfunction to schizophrenia and the prevalences of dysfunction among functionally psychotic and normal individuals. Therefore, we investigated pursuit tracking in a large sample of psychotic patients, normal subjects, and first-degree relatives (N = 482). Patients were recruited as part of an epidemiological study of first-episode psychosis that used a broadly based referral network to identify all cases in a major metropolitan area over a 2 1/2-year period. Patients received diagnoses of schizophrenia, schizophreniform disorder, psychotic mood disorder, and paranoid or other psychotic disorder based on the third edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1980). The distribution of tracking performance was bimodal for the schizophrenic patients and their relatives, perhaps reflecting major gene action. Moreover, poor tracking ran in families. Pursuit tracking dysfunction was relatively specific to schizophrenic patients and their relatives and occurred infrequently in other psychotic patients and normal subjects.     

A dimensional model of personality disorder: incorporating DSM Cluster A characteristics

The authors articulate an expanded dimensional model of personality pathology to better account for symptoms of DSM-defined Cluster A personality disorders. Two hundred forty participants (98 first-degree relatives of probands with schizophrenia or schizoaffective disorder, 92 community control participants, and 50 first-degree relatives of probands with bipolar disorder) completed a dimensional personality pathology questionnaire, a measure of schizotypal characteristics, and Chapman measures of psychosis proneness. Scales from all questionnaires were subjected to an exploratory factor analysis with varimax rotation. A 5-factor structure of personality pathology emerged from the analyses, with Peculiarity forming an additional factor to the common 4-factor structure of personality pathology (consisting of Introversion, Emotional Dysregulation, Antagonism, and Compulsivity). These results support a 5-factor dimensional model of personality pathology that better accounts for phenomena encompassed by the Cluster A personality disorders in DSM-IV-TR (4th ed., text revised; American Psychiatric Association, 2000). This study has implications for the consideration of a dimensional model of personality disorder in DSM-V by offering a more comprehensive structural model that builds on previous work in this area.     

Familial multiple sclerosis with repetitive relapses of manic psychosis in two patients (mother and daughter)

The clinical presentation of multiple sclerosis (MS) with psychiatric symptoms is uncommon but it is believed that MS patients are twice as likely to be afflicted with bipolar disorder as the general population. We report two cases (mother and daughter) of MS presenting with bipolar disorder in the form of recurrent manic psychosis and whose outcome was favourable with neuroleptics and corticosteroids. In both cases we found multiple hypersignal lesions on brain magnetic resonance imaging (MRI), especially in the right frontal lobe where we observed signs of activity. Apart from clinical and radiological concordance, the patients exhibited similar class I HLA alleles and identical class II HLA alleles. We focused discussion on whether there may be a common genetic susceptibility to both illnesses or whether MS caused psychiatric manifestations. The coincidence of psychiatric and neurological symptoms in most relapses supports the second hypothesis.     

The nature of schizotypy among multigenerational multiplex schizophrenia families

Identification of endophenotypes (Gottesman & Gould, 2003; Gottesman & Shields, 1972) that genetically correlate with schizophrenia and are genetically homogeneous is an important strategy for detecting genes that affect schizophrenia risk. Symptoms of schizotypy may familially correlate with schizophrenia; however, there are critical limitations of the current literature concerning this association. The present study examined the genetic architecture and genetic associations between schizotypy and schizophrenia among multigenerational, multiplex schizophrenia families. Genetic schizotypy factor scales were developed that genetically correlated with schizophrenia, although some relations were unexpected in direction suggesting minimization of "psychotic-like" symptoms. These genetic schizotypy factor scales did not genetically correlate with major depressive disorder or substance dependence indicating specificity to schizophrenia. The results highlight the possibility of significant response bias in schizophrenia families, particularly among close relatives, and suggest an important consideration when acquiring self-report information. This is a topic that deserves future study as the origins of this putative bias in relatives are unclear. In addition, the results support the identification of genetic schizotypy factors as a promising technique for maximizing genetic correlation of endophenotypes with schizophrenia.     

Immersion in altered experience: An investigation of the relationship between absorption and psychopathology

Understanding alterations in perceptual experiences as a component of the basic symptom structure of psychosis may improve early detection and the identification of subtle shifts that can precede symptom onset or exacerbation. We explored the phenomenological construct of absorption and psychotic experiences in both clinical (bipolar psychosis and schizophrenia spectrum) and non-clinical participants. Participants with psychosis endorsed significantly higher absorption compared to the non-clinical group. Absorption was positively correlated with all types of hallucinations and multiple types of delusions. The analysis yielded two distinct cluster groups that demarcated a distinction along the continuum of self-disturbance: on characterized by attenuated ego boundaries and the other stable ego boundaries. The study suggests that absorption is a potentially important but under-researched component of psychosis that overlaps with, but is not identical to the more heavily theorized constructs of aberrant salience and hyperreflexivity.     

Social anxiety and the shame of psychosis: a study in first episode psychosis

Social anxiety disorder (SaD) or social phobia is a co-morbid affective disorder in schizophrenia, present in up to one in three individuals. We employ 'social rank' theory to predict that one pathway to social anxiety in schizophrenia is triggered by the anticipation of a catastrophic loss of social status that the stigma of schizophrenia can entail. A group of 79 people with a first episode of psychosis were assessed for social anxiety: hypotheses were tested comparing 23 socially anxious and 56 non-anxious patients on measures of cognitive appraisals of shame/stigma of psychosis and perceived social status, controlling for depression, psychotic symptoms and general psychopathology. Participants with social anxiety experienced greater shame attached to their diagnosis and felt that the diagnosis placed them apart from others, i.e., socially marginalised them and incurred low social status. We propose a stigma model of social anxiety that makes testable predictions about how the shame beliefs may contaminate social interaction and thereby exacerbate and maintain social phobia.     

High Behavioral Approach System (BAS) sensitivity, reward responsiveness, and goal-striving predict first onset of bipolar spectrum disorders: a prospective behavioral high-risk design

A prospective, behavioral high-risk design provided a theoretically guided examination of vulnerability to first onset of bipolar spectrum disorder based on the Behavioral Approach System (BAS) model. Adolescents (ages 14-19) at an "age of risk" for bipolar disorder onset were screened on BAS sensitivity by interviewers blind to current symptoms, lifetime history, and family history of psychopathology. Participants were selected with high versus moderate levels of BAS sensitivity and administered a lifetime diagnostic interview. Those with a bipolar spectrum disorder, psychosis, or hypomanic episode with onset prior to the BAS sensitivity assessment were excluded. High BAS (n = 171) and moderate BAS (n = 119) sensitivity participants in the final sample completed baseline measures of symptoms, goal-setting, and reward responsiveness and were followed prospectively with semistructured diagnostic interviews every 6 months. Consistent with the vulnerability hypothesis of the BAS model of bipolar disorder, high BAS participants had a greater likelihood, and shorter time to onset, of bipolar spectrum disorder than moderate BAS participants across an average of 12.8 months of follow-up (12.9% vs. 4.2%), controlling for baseline depressive and hypomanic symptoms, and family history of bipolar disorder. High reward responsiveness on a behavioral task and ambitious goal-striving for popular fame and financial success (but not impulsivity) also predicted first onset of bipolar spectrum disorder controlling for the covariates and BAS risk group, and ambitious goal-striving partially mediated the BAS risk group effect. We discuss implications of the findings for the BAS model of bipolar disorder and early intervention efforts.     

A mind to go out of: reflections on primary and secondary consciousness

Dreaming and waking are two brain-mind states, which are characterized by shared and differentiated properties at the levels of brain and consciousness. As part of our effort to capitalize on a comparison of these two states we have applied Edelman's distinction between primary and secondary consciousness, which we link to dreaming and waking respectively. In this paper we examine the implications of this contrastive analysis for theories of mental illness. We conclude that while dreaming is an almost perfect model of organic psychosis, it is less so for schizophrenia and major affective disorder where it must serve a primarily heuristic role helping us to model hallucinations and delusions but not the diseases themselves.     

Psychosis and autism as diametrical disorders of the social brain

Autistic-spectrum conditions and psychotic-spectrum conditions (mainly schizophrenia, bipolar disorder, and major depression) represent two major suites of disorders of human cognition, affect, and behavior that involve altered development and function of the social brain. We describe evidence that a large set of phenotypic traits exhibit diametrically opposite phenotypes in autistic-spectrum versus psychotic-spectrum conditions, with a focus on schizophrenia. This suite of traits is inter-correlated, in that autism involves a general pattern of constrained overgrowth, whereas schizophrenia involves undergrowth. These disorders also exhibit diametric patterns for traits related to social brain development, including aspects of gaze, agency, social cognition, local versus global processing, language, and behavior. Social cognition is thus underdeveloped in autistic-spectrum conditions and hyper-developed on the psychotic spectrum.;>We propose and evaluate a novel hypothesis that may help to explain these diametric phenotypes: that the development of these two sets of conditions is mediated in part by alterations of genomic imprinting. Evidence regarding the genetic, physiological, neurological, and psychological underpinnings of psychotic-spectrum conditions supports the hypothesis that the etiologies of these conditions involve biases towards increased relative effects from imprinted genes with maternal expression, which engender a general pattern of undergrowth. By contrast, autistic-spectrum conditions appear to involve increased relative bias towards effects of paternally expressed genes, which mediate overgrowth. This hypothesis provides a simple yet comprehensive theory, grounded in evolutionary biology and genetics, for understanding the causes and phenotypes of autistic-spectrum and psychotic-spectrum conditions.     

Investigating the M-FAST: psychometric properties and utility to detect diagnostic specific malingering

This study examined the ability of the M-FAST to differentiate a group of undergraduate students simulating one of four DSM-IV diagnoses (n = 190; schizophrenia, major depressive disorder, bipolar disorder, and posttraumatic stress disorder) and a clinical comparison sample drawn from previous M-FAST studies comprising individuals with the same diagnosis (n = 142). Across all diagnostic conditions, the simulators obtained higher M-FAST total scores than the clinical comparisons, and the rare combinations scale was equal or superior to the total score at differentiating the groups. The M-FAST was most efficient at distinguishing feigned from bona fide schizophrenia. Although the internal consistency of the total score was high (alpha = 0.88), inter-item correlations were lower than values reported in previous research. Lastly, given the importance of base rate considerations in the evaluation of diagnostic instruments, it was notable that the M-FAST was able to identify malingerers even at relatively low base rates.     

Perceived Genetic Risks for Bipolar Disorder in a Patient Population: An Exploratory Study

Thirty-one subjects with bipolar illness completed a questionnaire about genetic risk for bipolar disorder. Subjects estimated both quantitative and qualitative genetic risk for bipolar disorder for the following categories: general population, siblings, parents, spouses, and children. Results showed that quantitative risks were inflated when compared to qualitative risks and that subjects routinely overestimated the risk for developing bipolar illness. These findings suggest that genetic counseling may be useful for this population.