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 Children's 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.

A mentalization-based approach to the development of the therapeutic alliance in the treatment of schizophrenia.

This article presents a clinical illustration of a mentalization-based approach to the development of a therapeutic alliance in the treatment of schizophrenia. A clinically focused overview of the attachment-based understanding of mentalization central to the mentalization-based treatment model is first provided. This is followed by a brief summary of the theory and evidence supporting the possible link between attachment disturbances and deficits of mental state understanding in schizophrenia. A case presentation then illustrates the application of core mentalization-based principles and interventions to enhance the therapeutic alliance by addressing disruptions of mentalization and reducing paranoia in the treatment of a patient with early course schizophrenia.

Neural responses during social reflection in relatives of schizophrenia patients: relationship to subclinical delusions.

BACKGROUND: Deficits in the capacity to reflect about the self and others ("social reflection" [SR]) have been identified in schizophrenia, as well as in people with a genetic or clinical risk for the disorder. However, the neural underpinnings of these abnormalities are incompletely understood. METHODS: Responses of a network of brain regions known to be involved in self and other processing (e.g., medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and superior temporal gyrus (STG)) were measured during SR in 16 first-degree, non-psychotic relatives (RELS) of schizophrenia patients and 16 healthy controls (CONS). Because of prior evidence linking dysfunction in this network and delusions, associations between SR-related responses of this network and subclinical delusions (measured using the Peters et al. Delusions Inventory) were also examined. RESULTS: Compared with CONS, RELS showed significantly less SR-related activity of the right and left PCC and STG. Moreover, response magnitudes were negatively correlated with levels of delusional thinking across both groups. CONCLUSIONS: These findings suggest that aberrant function of the neural circuitry underpinning SR is associated with the genetic liability to schizophrenia and confers vulnerability to delusional beliefs.

Mentalization-based treatment for psychosis: linking an attachment-based model to the psychotherapy for impaired mental state understanding in people with psychotic disorders.

Disturbances of mentalization have been increasingly associated with the symptoms and functional impairment of people with psychotic disorders. it has been proposed that psychotherapy designed to foster self and other understanding, such as mentalization-based treatment (mBt), may play an important part in facilitating recovery from psychosis. Here, we present an attachment-based understanding of mentalization impairments. We then outline a neuropsychological model that links disruptions of mentalization associated with disturbances in the caregiving environment to the pathophysiology of psychosis in genetically at-risk individuals. this is followed by an illustration of some of the core mBt techniques for the rehabilitation of the capacity to mentalize as applied to the treatment of a patient with a psychotic disorder.

Subclinical delusional thinking predicts lateral temporal cortex responses during social reflection.

Neuroimaging studies have demonstrated associations between delusions in psychotic disorders and abnormalities of brain areas involved in social cognition, including medial prefrontal cortex (MPFC), posterior cingulate cortex, and lateral temporal cortex (LTC). General population studies have linked subclinical delusional thinking to impaired social cognition, raising the question of whether a specific pattern of brain activity during social perception is associated with delusional beliefs. Here, we tested the hypothesis that subclinical delusional thinking is associated with changes in neural function, while subjects made judgments about themselves or others ['social reflection' (SR)]. Neural responses during SR and non-social tasks, as well as resting-state activity, were measured using functional magnetic resonance imaging in 22 healthy subjects. Delusional thinking was measured using the Peters et al. Delusions Inventory. Delusional thinking was negatively correlated with responses of the left LTC during SR (r = -0.61, P = 0.02, Bonferroni corrected), and connectivity between the left LTC and left ventral MPFC, and was positively correlated with connectivity between the left LTC and the right middle frontal and inferior temporal cortices. Thus, delusional thinking in the general population may be associated with reduced activity and aberrant functional connectivity of cortical areas involved in SR.

Self-disturbances as a possible premorbid indicator of schizophrenia risk: a neurodevelopmental perspective.

Self-disturbances (SDs) are increasingly identified in schizophrenia and are theorized to confer vulnerability to psychosis. Neuroimaging research has shed some light on the neural correlates of SDs in schizophrenia. But, the onset and trajectory of the neural alterations underlying SDs in schizophrenia remain incompletely understood. We hypothesize that the aberrant structure and function of brain areas (e.g., prefrontal, lateral temporal, and parietal cortical structures) comprising the "neural circuitry of self" may represent an early, premorbid (i.e., pre-prodromal) indicator of schizophrenia risk. Consistent with neurodevelopmental models, we argue that "early" (i.e., perinatal) dysmaturational processes (e.g., abnormal cortical neural cell migration and mini-columnar formation) affecting key prefrontal (e.g., medial prefrontal cortex), lateral temporal cortical (e.g., superior temporal sulcus), and parietal (e.g., inferior parietal lobule) structures involved in self-processing may lead to subtle disruptions of "self" during childhood in persons at risk for schizophrenia. During adolescence, progressive neurodevelopmental alterations (e.g., aberrant synaptic pruning) affecting the neural circuitry of self may contribute to worsening of SDs. This could result in the emergence of prodromal symptoms and, eventually, full-blown psychosis. To highlight why adolescence may be a period of heightened risk for SDs, we first summarize the literature regarding the neural correlates of self in typically developing children. Next, we present evidence from neuroimaging studies in genetic high-risk youth suggesting that fronto-temporal-parietal structures mediating self-reflection may be abnormal in the premorbid period. Our goal is that the ideas presented here might provide future directions for research into the neurobiology of SDs during the pre-psychosis development of youth at risk for schizophrenia.

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.

Insight into illness in patients and caregivers during early psychosis: a pilot study.

BACKGROUND: Impaired insight into illness is common during early psychosis and has been associated with treatment delays and poorer long-term outcomes. The relationship between patients' insight into illness and their caregivers' knowledge about psychosis is putatively associated with treatment outcome but there is limited research about this. This pilot study was designed to test the hypothesis that caregivers' levels of insight into illness is associated with patients' insight into illness in early psychosis and would be related to caregivers' levels of critical, rejecting attitudes toward patients. METHODS: Patients with schizophrenia or schizoaffective disorder within 5 years of psychosis onset (n=14) and caregivers (n=14) of the patients' choosing were studied. Insight into illness was assessed in patients using the Scale to assess Unawareness of Mental Disorder (SUMD). Caregiver insight into illness was assessed with a modified version of the SUMD with questions rephrased to probe caregivers' understanding of the patients' illness. Caregivers' critical attitudes toward patients were assessed with the Patient Rejection Scale (PRS). RESULTS: Significant correlations were found between patients' and caregivers' awareness of need for treatment (r=.55, p=.02), awareness of symptoms (r=.48, p=.04) and between caregivers' awareness of illness and critical attitudes toward patients (r=.65, p=.01). CONCLUSIONS: These findings suggest that caregivers' emotional characteristics and levels of insight into illness may be related to insight into illness in patients. Implications for family psychoeducational approaches to impairments of insight into illness during early psychosis are discussed.

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.

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.

Psychotic-spectrum illness and family-based treatments: a case-based illustration of the underuse of family interventions.

Psychotic-spectrum illnesses (PSIs) are a significant cause of relational dysfunction and vocational disability, and result in substantial economic costs to society. The impact of family process, particularly "expressed emotion," on influencing the relapse rate of PSIs is now well documented. Over the last two decades, evidence has emerged supporting family-based treatments that decrease family stress (e.g., psychoeducation, training in problem solving, and improved communication), reduce the relapse rate, and improve medication adherence and social functioning among patients with PSIs. Family interventions are now included in the Expert Consensus Guidelines and the Agency for Health Care Policy and Research/National Institute of Mental Health (AHCPR/NIMH) Schizophrenia Patient Outcomes Research Team (PORT) recommendations for the treatment of schizophrenia. Nevertheless, family-based treatments are underused in the care of PSI patients. Building upon a case example, this article explores the barriers to implementing family interventions in the acute and outpatient treatment of these patients. The case discussion highlights the convergence of problems in the mental health care system with clinicians' typical capacities and practices, difficulties intrinsic to the nature of PSI itself, and the burden and stigmatization of families of the severely mentally ill. Taken together, these factors undercut the implementation of evidence-based family interventions.