Benjamin K. Brent

A review of neuroimaging studies of young relatives of individuals with schizophrenia: A developmental perspective from schizotaxia to schizophrenia

In an effort to identify the developing abnormalities preceding psychosis, Dr. Ming T. Tsuang and colleagues at Harvard expanded Meehls concept of “schizotaxia,” and examined brain structure and function in families affected by schizophrenia (SZ). Here, we systematically review genetic (familial) high‐risk (HR) studies of SZ using magnetic resonance imaging (MRI), examine how findings inform models of SZ etiology, and suggest directions for future research. Neuroimaging studies of youth at HR for SZ through the age of 30 were identified through a MEDLINE (PubMed) search. There is substantial evidence of gray matter volume abnormalities in youth at HR compared to controls, with an accelerated volume reduction over time in association with symptoms and cognitive deficits. In structural neuroimaging studies, prefrontal cortex (PFC) alterations were the most consistently reported finding in HR. There was also consistent evidence of smaller hippocampal volume. In functional studies, hyperactivity of the right PFC during performance of diverse tasks with common executive demands was consistently reported. The only longitudinal fMRI study to date revealed increasing left middle temporal activity in association with the emergence of psychotic symptoms. There was preliminary evidence of cerebellar and default mode network alterations in association with symptoms. Brain abnormalities in structure, function and neurochemistry are observed in the premorbid period in youth at HR for SZ. Future research should focus on the genetic and environmental contributions to these alterations, determine how early they emerge, and determine whether they can be partially or fully remediated by innovative treatments.

Subarachnoid hemorrhage incidence among whites, blacks and caribbean hispanics: The Northern Manhattan Study

American blacks and Hispanics may have a greater incidence of subarachnoid hemorrhage (SAH) than whites, but incidence data are scant. We used an active hospital and community surveillance program and autopsy reports to identify incident SAH cases among white, black and Hispanic adults living in Northern Manhattan between July 1993 and June 1997. The annual incidence adjusted for age and sex to the 1990 US Census was 9.7 per 100,000 (95% CI 7.5–12.0). Compared with whites (9 cases, age- and sex-adjusted annual incidence 8.2 per 100,000), the rate ratio of SAH was 1.3 (95% CI 0.7–2.4) for Hispanics (34 cases, incidence 10.9), and 1.6 (95% CI 0.8–2.8) for blacks (9 cases, incidence 12.8). The 30-day case fatality rate was 26%. Risk of death increased significantly with age and severity at onset but was not influenced by gender or race-ethnicity.

Mentalization-based psychodynamic psychotherapy for psychosis.

This article discusses and illustrates the use of mentalization-based psychodynamic psychotherapy for disturbances of awareness of the self and others in patients with psychotic-spectrum disorders. The literature on impairments of mental processes involved in self-awareness and awareness of others occurring in psychotic illnesses and the relationship between childhood trauma and the emergence of psychotic symptoms is reviewed. A case illustrates how mentalization-based treatment can facilitate treatment engagement and be used to manage enactments in the psychotherapy with a patient with a psychotic disorder. Mentalization-based psychotherapy may offer a useful adjunct to antipsychotic medication and psychosocial evidence-based treatments in the care of individuals in the early phase of psychotic disorders.

Gray Matter Alterations in Schizophrenia High-Risk Youth and Early-Onset Schizophrenia: A Review of Structural MRI Findings

This article reviews the literature on structural magnetic resonance imaging findings in pediatric and young adult populations at clinical or genetic high-risk for schizophrenia and early-onset schizophrenia. The implications of this research are discussed for understanding the pathophysiology of schizophrenia and for early intervention strategies. The evidence linking brain structural changes in prepsychosis development and early-onset schizophrenia with disruptions of normal neurodevelopmental processes during childhood or adolescence is described. Future directions are outlined for research to address knowledge gaps regarding the neurobiological basis of brain structural abnormalities in schizophrenia and to improve the usefulness of these abnormalities for preventative interventions.

Differential processing of metacognitive evaluation and the neural circuitry of the self and others in schizophrenia: A pilot study

BACKGROUND Impaired awareness of the self and others (i.e., metacognitive evaluations) are seen in schizophrenia. We compared patterns of activation in schizophrenia (SZ) and nonclinical subjects during a functional magnetic resonance imaging (fMRI) task of metacognitive evaluations that has been demonstrated to engage the neural circuitry of the self in healthy subjects. METHODS Eleven SZ subjects (7 males, mean age 26.6+/-8) and 10 healthy control subjects (4 males, mean age 29.6+/-8.4) were enrolled. Participants completed two runs of a metacognitive evaluation task (self vs. other vs. word meaning). fMRI data was obtained using a full body Bruker MedSped 4.0Tesla system. Group contrasts were performed using an uncorrected p<0.005 with a 50voxel extent threshold. RESULTS We observed a significant hypoactivation in the left superior temporal sulcus (STS) during metacognitive evaluations of others (OE) vs. semantic positivity evaluations (SPE) and a trend toward significant hypoactivation in the OE vs. self evaluations (SE) in the SZ group. Significant hypoactivation was also seen in the right inferior temporal gyrus (ITG) in the OE vs. SE contrasts in the SZ group. A trendworthy hypoactivation was seen in the SZ group in the right middle frontal gyrus and pole of the left STS during OE vs. SPE and SE contrasts respectively. CONCLUSIONS These results extend previous findings of impaired metacognitive evaluative processes in schizophrenia to aberrations of the neural circuitry implicated in self/other awareness among SZ patients. Greater understanding of the neural basis of deficits of self/other awareness in early schizophrenia may contribute to improvements in the identification and treatment of individuals at risk for the illness.

A Mentalization-Based Treatment Approach to Disturbances of Social Understanding in Schizophrenia

Mentalization (i.e., the ability to think about states of mind (e.g., thoughts, feelings, intentions) in the self and other people) and metacognition (‘thinking about thinking’) have increasingly been linked both theoretically and empirically, as both constructs involve the capacity for meta-representation within social contexts. Promising evidence is emerging for the value of metacognitive psychotherapy in the treatment of people with schizophrenia. In this chapter, we present the rationale for adapting a mentalization-based treatment (MBT) approach to the recovery of mental state understanding in schizophrenia.

Neurobiology of self-awareness deficits in schizophrenia: A hypothetical model

Self-awareness (SA) is a cognitive ability to differentiate between self and non-self cues and is pivotal to understand the behavior of other human beings. For this reason, there has been a significant interest to investigate the neurobiology of SA in human subjects. So far the majority of such research has been conducted in healthy subjects but a significant relationship between impaired SA and poor psychosocial outcome in schizophrenia has stimulated neuroimaging research in this patient population. The results from small number of neuroimaging studies in schizophrenia suggest that impaired SA may be mediated by a dysfunction of cortical midline structures. This paper is an attempt to review emerging functional magnetic resonance imaging (fMRI) data in schizophrenia and to propose a hypothetical model of deficits in SA in schizophrenia that can be tested in future research. The model is refined from the available literature and proposes that self-referential activity appears to reflect a shift from activation of anterior to posterior cortical midline structures in schizophrenia subjects, which may be related to lack of functional connectivity between different cortical midline regions.

Attachment, Neurobiology, and Mentalizing along the Psychosis Continuum

In this review article, we outline the evidence linking attachment adversity to psychosis, from the premorbid stages of the disorder to its clinical forms. To better understand the neurobiological mechanisms through which insecure attachment may contribute to psychosis, we identify at least five neurobiological pathways linking attachment to risk for developing psychosis. Besides its well documented influence on the hypothalamic-pituary-adrenal (HPA) axis, insecure attachment may also contribute to neurodevelopmental risk through the dopaminergic and oxytonergic systems, as well as bear influence on neuroinflammation and oxidative stress responses. We further consider the neuroscientific and behavioral studies that underpin mentalization as a suite of processes potentially moderating the risk to transition to psychotic disorders. In particular, mentalization may help the individual compensate for endophenotypical impairments in the integration of sensory and metacognitive information. We propose a model where embodied mentalization would lie at the core of a protective, resilience response mitigating the adverse and potentially pathological influence of the neurodevelopmental cascade of risk for psychosis.

Alterations of lateral temporal cortical gray matter and facial memory as vulnerability indicators for schizophrenia: An MRI study in youth at familial high-risk for schizophrenia

BACKGROUND Structural alterations of the lateral temporal cortex (LTC) in association with memory impairments have been reported in schizophrenia. This study investigated whether alterations of LTC structure were linked with impaired facial and/or verbal memory in young first-degree relatives of people with schizophrenia and, thus, may be indicators of vulnerability to the illness. METHODS Subjects included 27 non-psychotic, first-degree relatives of schizophrenia patients, and 48 healthy controls, between the ages of 13 and 28. Participants underwent high-resolution magnetic resonance imaging (MRI) at 1.5Tesla. The LTC was parcellated into superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and temporal pole. Total cerebral and LTC volumes were measured using semi-automated morphometry. The Wechsler Memory Scale - Third Edition and the Childrens Memory Scale - Third Edition assessed facial and verbal memory. General linear models tested for associations among LTC subregion volumes, familial risk and memory. RESULTS Compared with controls, relatives had significantly smaller bilateral middle temporal gyri. Moreover, right middle temporal gyral volume showed a significant positive association with delayed facial memory in relatives. CONCLUSION These results support the hypothesis that smaller middle temporal gyri are related to the genetic liability to schizophrenia and may be linked with reduced facial memory in persons at genetic risk for the illness. The findings add to the growing evidence that children at risk for schizophrenia on the basis of positive family history have cortical and subcortical structural brain abnormalities well before psychotic illness occurs.