Faculty Bibliography

BACKGROUND:Identifying individuals at increased risk of suicide is important, particularly those who present for treatment for nonpsychiatric chief complaints who may go undetected. It has been found that pain symptoms, such as headache, are associated with suicide, although this association requires further characterization. This study examined specific components of suicidality in relation to headache subtypes. METHODS:This study retrospectively reviewed 2,832,835 nonpsychiatric adult clinical encounters at a large county hospital, where a standardized suicide risk screening tool, the Columbia-Suicide Severity Rating Scale (C-SSRS), was universally implemented. The C-SSRS assesses specific components of suicidality: wish to be dead and suicidal ideation, method, intent, plan, and action. Multivariate logistic regressions were performed to assess the association between headache, as well as headache subtype (migraine, tension, or cluster), and each component of suicidality. RESULTS:There were significant positive associations between presenting with a headache and 2 specific components of suicidality: wish to be dead and suicidal action. Individuals with tension headache may have a lower risk of wishing to be dead compared to those with migraine and cluster headaches. CONCLUSIONS:The association of headaches with specific elements of sui-cidality demonstrates the potential yield of identification of suicide risk among individuals with nonpsychiatric presentations.

Schizophrenia is a disorder of altered neural connections resulting in impaired information integration. Whole brain assessment of within- and between-network connections may determine how information processing is disrupted in schizophrenia. Patients with early-stage schizophrenia (n = 56) and a matched control sample (n = 32) underwent resting-state fMRI scans. Gray matter regions were organized into nine distinct functional networks. Functional connectivity was calculated between 278 gray matter regions for each subject. Network connectivity properties were defined by the mean and variance of correlations of all regions. Whole-brain network measures of global efficiency (reflecting overall interconnectedness) and locations of hubs (key regions for communication) were also determined. The control sample had greater connectivity between the following network pairs: somatomotor-limbic, somatomotor-default mode, dorsal attention-default mode, ventral attention-limbic, and ventral attention-default mode. The patient sample had greater variance in interactions between ventral attention network and other functional networks. Illness duration was associated with overall increases in the variability of network connections. The control group had higher global efficiency and more hubs in the cerebellum network, while patient group hubs were more common in visual, frontoparietal, or subcortical networks. Thus, reduced functional connectivity in patients was largely present between distinct networks, rather than within-networks. The implications of these findings for the pathophysiology of schizophrenia are discussed.

Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

Metacognition refers to a range of cognitive processes that allow one to form complex ideas of self and others and to use this information to navigate psychosocial challenges. Several studies in both early-phase and prolonged schizophrenia have demonstrated not only that significant deficits in metacognitive ability are present, but importantly that they are associated with significant functional impairment and decreased quality of life. In spite of the importance of metacognitive impairment in schizophrenia, relatively little is known about the biological substrates that may contribute to this dysfunction. In this study, we examined the relationship between resting state functional connectivity of the medial prefrontal cortex (mPFC), a structure shown in prior voxel-based morphometry studies to be associated with metacognition, with metacognitive function in an early-phase psychosis cohort (n=18). Analyses revealed a positive association of resting state functional connectivity between the mPFC and precuneus and posterior cingulate structures and metacognitive ability. These results provide evidence of disrupted resting state connectivity in structures relevant to metacognitive dysfunction in early-phase psychosis, which may have implications for pathophysiological models of complex cognitive deficits in this illness.