The importance of covert memory consolidation in schizophrenia: Dysfunctional network profiles of the hippocampus and the dorsolateral prefrontal cortex.

Altered brain network profiles in schizophrenia (SCZ) during memory consolidation are typically observed during task-active periods such as encoding or retrieval. However active processes are also sub served by covert periods of memory consolidation. These periods are active in that they allow memories to be recapitulated even in the absence of overt sensorimotor processing. It is plausible that regions central to memory formation like the dlPFC and the hippocampus, exert network signatures during covert periods. Are these signatures altered in patients? The question is clinically relevant because real world learning and memory is facilitated by covert processing, and may be impaired in schizophrenia. Here, we compared network signatures of the dlPFC and the hippocampus during covert periods of a learning and memory task. Because behavioral proficiency increased non-linearly, functional connectivity of the dlPFC and hippocampus [psychophysiological interaction (PPI)] was estimated for each of the Early (linear increases in performance) and Late (asymptotic performance) covert periods. During Early periods, we observed hypo-modulation by the hippocampus but hyper-modulation by dlPFC. Conversely, during Late periods, we observed hypo-modulation by both the dlPFC and the hippocampus. We stitch these results into a conceptual model of network deficits during covert periods of memory consolidation.

Learning without contingencies: A loss of synergy between memory and reward circuits in schizophrenia.

Motivational deficits in schizophrenia may interact with foundational cognitive processes including learning and memory to induce impaired cognitive proficiency. If such a loss of synergy exists, it is likely to be underpinned by a loss of synchrony between the brains learning and reward sub-networks. Moreover, this loss should be observed even during tasks devoid of explicit reward contingencies given that such tasks are better models of real world performance than those with artificial contingencies. Here we applied undirected functional connectivity (uFC) analyses to fMRI data acquired while participants engaged in an associative learning task without contingencies or feedback. uFC was estimated and inter-group differences (between schizophrenia patients and controls, n = 54 total, n = 28 patients) were assessed within and between reward (VTA and NAcc) and learning/memory (Basal Ganglia, DPFC, Hippocampus, Parahippocampus, Occipital Lobe) sub-networks. The task paradigm itself alternated between Encoding, Consolidation, and Retrieval conditions, and uFC differences were quantified for each of the conditions. Significantly reduced uFC dominated the connectivity profiles of patients across all conditions. More pertinent to our motivations, these reductions were observed within and across classes of sub-networks (reward-related and learning/memory related). We suggest that disrupted functional connectivity between reward and learning sub-networks may drive many of the performance deficits that characterize schizophrenia. Thus, cognitive deficits in schizophrenia may in fact be underpinned by a loss of synergy between reward-sensitivity and cognitive processes.

The topology, stability, and instability of learning-induced brain network repertoires in schizophrenia.

There is a paucity of graph theoretic methods applied to task-based data in schizophrenia (SCZ). Tasks are useful for modulating brain network dynamics, and topology. Understanding how changes in task conditions impact inter-group differences in topology can elucidate unstable network characteristics in SCZ. Here, in a group of patients and healthy controls (n = 59 total, 32 SCZ), we used an associative learning task with four distinct conditions (Memory Formation, Post-Encoding Consolidation, Memory Retrieval, and Post-Retrieval Consolidation) to induce network dynamics. From the acquired fMRI time series data, betweenness centrality (BC), a metric of a node's integrative value was used to summarize network topology in each condition. Patients showed (a) differences in BC across multiple nodes and conditions; (b) decreased BC in more integrative nodes, but increased BC in less integrative nodes; (c) discordant node ranks in each of the conditions; and (d) complex patterns of stability and instability of node ranks across conditions. These analyses reveal that task conditions induce highly variegated patterns of network dys-organization in SCZ. We suggest that the dys-connection syndrome that is schizophrenia, is a contextually evoked process, and that the tools of network neuroscience should be oriented toward elucidating the limits of this dys-connection.

Basal glutamate in the hippocampus and the dorsolateral prefrontal cortex in schizophrenia: Relationships to cognitive proficiency investigated with structural equation modelling.

OBJECTIVES: Schizophrenia is characterised by deficits across multiple cognitive domains and altered glutamate related neuroplasticity. The purpose was to investigate whether glutamate deficits are related to cognition in schizophrenia, and whether glutamate-cognition relationships are different between schizophrenia and controls. METHODS: Magnetic resonance spectroscopy (MRS) at 3 Tesla was acquired from the dorsolateral prefrontal cortex (dlPFC) and hippocampus in 44 schizophrenia participants and 39 controls during passive viewing visual task. Cognitive performance (working memory, episodic memory, and processing speed) was assessed on a separate session. Group differences in neurochemistry and mediation/moderation effects using structural equation modelling (SEM) were investigated. RESULTS: Schizophrenia participants showed lower hippocampal glutamate (p = .0044) and myo-Inositol (p = .023) levels, and non-significant dlPFC levels. Schizophrenia participants also demonstrated poorer cognitive performance (p < .0032). SEM-analyses demonstrated no mediation or moderation effects, however, an opposing dlPFC glutamate-processing speed association between groups was observed. CONCLUSIONS: Hippocampal glutamate deficits in schizophrenia participants are consistent with evidence of reduced neuropil density. Moreover, SEM analyses indicated that hippocampal glutamate deficits in schizophrenia participants as measured during a passive state were not driven by poorer cognitive ability. We suggest that functional MRS may provide a better framework for investigating glutamate-cognition relationships in schizophrenia.

Predictors of Retention and Drug Use Among Patients With Opioid Use Disorder Transferred to a Specialty "Second Chance" Methadone Program.

Background: Many patients in methadone treatment have difficulty achieving or maintaining drug abstinence, and many clinics have policies that lead to discharging these patients. We designed a pilot "Second Chance" (SC) program for patients scheduled to be discharged from other local methadone clinics to be transferred to our clinic. Aim: Determine whether SC patients' retention and opioid use is related to physical or mental health conditions, non-opioid substance use, or treatment features. Methods: From December 2012 to December 2014, this program enrolled 70 patients who were discharged from other clinics in the area; we were their last remaining option for methadone treatment. Unlike the clinic's standard policies, the treatment focus for SC patients was retention rather than abstinence. This program focused on connection to care (eg, psychiatric services) and enabled patients to continue receiving services despite ongoing substance use. Each patient was assessed at treatment entry and followed until June 2016 to evaluate outcomes. Results: SC patients receiving disability benefits (n = 37) vs. non-disabled (n = 33) had significantly (P < .05) higher rates of current DSM-IV Axis I psychiatric diagnosis (97% vs 70%), prescriptions for opioids (84% vs 55%) and benzodiazepines (65% vs 27%), and higher methadone doses at admission (58 vs 46 mg) but did not differ significantly in rates of 6-month or 1-year retention (77% and 56%, respectively) or all-drug use (39% positive urine drug screens). Methadone doses >65 mg predicted significantly longer retention and less opioid use, but these effects were not moderated by baseline characteristics. Conclusions: Patients in methadone treatment struggling to achieve abstinence may benefit from retention-oriented harm-reduction programs. Higher methadone doses can improve retention and opioid abstinence despite psychiatric comorbidities. Further work is needed to improve program implementation and outcomes in this complex population.

Disordered directional brain network interactions during learning dynamics in schizophrenia revealed by multivariate autoregressive models.

Directional network interactions underpin normative brain function in key domains including associative learning. Schizophrenia (SCZ) is characterized by altered learning dynamics, yet dysfunctional directional functional connectivity (dFC) evoked during learning is rarely assessed. Here, nonlinear learning dynamics were induced using a paradigm alternating between conditions (Encoding and Retrieval). Evoked fMRI time series data were modeled using multivariate autoregressive (MVAR) models, to discover dysfunctional direction interactions between brain network constituents during learning stages (Early vs. Late), and conditions. A functionally derived subnetwork of coactivated (healthy controls [HC] ∩ SCZ] nodes was identified. MVAR models quantified directional interactions between pairs of nodes, and coefficients were evaluated for intergroup differences (HC ≠ SCZ). In exploratory analyses, we quantified statistical effects of neuroleptic dosage on performance and MVAR measures. During Early Encoding, SCZ showed reduced dFC within a frontal-hippocampal-fusiform network, though during Late Encoding reduced dFC was associated with pathways toward the dorsolateral prefrontal cortex (dlPFC). During Early Retrieval, SCZ showed increased dFC in pathways to and from the dorsal anterior cingulate cortex, though during Late Retrieval, patients showed increased dFC in pathways toward the dlPFC, but decreased dFC in pathways from the dlPFC. These discoveries constitute novel extensions of our understanding of task-evoked dysconnection in schizophrenia and motivate understanding of the directional aspect of the dysconnection in schizophrenia. Disordered directionality should be investigated using computational psychiatric approaches that complement the MVAR method used in our work.

Inflammation and Trauma-Related Psychopathology in Syrian and Iraqi Refugees.

Refugees experience high rates of post-traumatic stress disorder (PTSD), anxiety, and depression due to exposure to civilian war trauma and forced migration. Inflammatory products may offer viable biological indicators of trauma-related psychopathology in this cohort, promoting rapid and objective assessment of psychopathology. Incoming Syrian and Iraqi refugees (n = 36) ages 18-65 completed self-report measures of PTSD, anxiety, and depression and provided saliva samples during an assessment at a primary care clinic within the first month of resettlement in the United States. Interleukin 1ß (IL-1ß) and C-reactive protein (CRP) differentially correlated with symptom severity by domain, and there was a non-significant trend for sex moderating the relation between inflammation and PTSD symptoms. Our findings show unique relations between trauma-related psychopathology and inflammation. There is a need for further research in diverse ethnic cohorts with differential trauma exposures for inflammation to be considered a biological indicator of psychopathology.

Prevalence of Possible Mental Disorders in Syrian Refugees Resettling in the United States Screened at Primary Care.

Little is known about mental health problems among newly arrived Syrian refugees in the US. It is important to determine the prevalence of common consequences of exposure to trauma and high stress, and provide needed interventions, as these conditions if untreated, can be detrimental to mental and physical health. Adult Syrian refugees (n = 157, 47.1% women, 52.9% men) were screened at one-month mandatory primary care health visit for Posttraumatic Stress Disorder (PTSD), anxiety and depression using PTSD Checklist, and Hopkins Symptoms Checklist. Prevalence of possible diagnoses was high for PTSD (32.2%), anxiety (40.3%), and depression (47.7%). Possible prevalence of depression and anxiety were higher among women, but there was no gender difference for possible PTSD. We found a high prevalence of possible psychiatric disorders related to trauma and stress among Syrian refugees newly resettled in the US. Due to the high prevalence and feasibility of brief screening tools in primary care facilities, we recommend mental health screening during primary care health visits for resettled Syrian refugees.

Characteristics and Triage of Children Presenting in Mental Health Crisis to Emergency Departments at Detroit Regional Hospitals.

OBJECTIVES: The number of children in the United States utilizing emergency department (ED) services for psychiatric crises is increasing, and psychiatric-related ED visits disproportionately burden hospital resources. Yet, there is limited available information on the epidemiology and outcomes of pediatric mental health emergencies. The present study sought to characterize pediatric mental health-related ED presentations in a large urban center and identify factors predictive of inpatient hospitalization. METHODS: Data were analyzed from a sample of 225 children (120 female and 105 male children), aged 5 to 18 years, who presented in mental health crisis to Detroit regional EDs over a 27-month period. A trained mental health professional used the Crisis Assessment Tool to assess all children. RESULTS: Thirty-eight percent of children presented with severe depression symptoms, and 52% were judged to be at acute risk of suicide, most of whom were female. Sixteen percent of the sample presented with severe psychotic features, and 34% were assessed as being at risk of harming others. Following assessment, 86% of the sample was directed to inpatient treatment, and no sex differences were found in treatment disposition. Risk of suicide, poor judgment, symptoms of psychosis, and risk of danger to others were all found to be significant predictors of subsequent inpatient hospitalization. CONCLUSIONS: Results provide descriptive information regarding child psychiatric emergency presentations in the city of Detroit. The identified factors that help determine triage to inpatient hospitalization suggest areas for possible resource allocation and potential ED-based intervention.

Training for Direct Support Staff at Group Homes for People with Chronic Mental Illness.

For people with chronic mental illness, their support system (including direct support staff at group homes) play a key role in ameliorating exacerbations leading to crisis care. However, little information exists on curriculum or training programs focused on reducing exacerbations while promoting compassionate care. We developed, implemented and evaluated such a program that featured role-playing and animated videos supplemented with limited didactics. During development phase, direct support staff reviewed videos and rated them as depicting realistic situations with high acceptability. During implementation, the 6-week course (at least one staff from six different group homes not involved in the development phase) using a 3-month pre-post design found reductions in total number of incident reports and pre-specified outcomes of recipient right complaints, emergency calls, and psychiatric hospitalizations. The program demonstrated acceptability, improved care and better outcomes on some but not all outcomes. Improved training of direct support staff is possible and has positive outcomes.

Home-Based Telepsychiatry in US Urban Area.

Telepsychiatry expands access to psychiatric care. However, telepsychiatry for elderly adults is only reimbursed in the US if the patient is assessed while in a clinical setting. This case study presents a homebound older woman previously hospitalized for schizophrenia who had not seen a psychiatrist in over 20 years. Care was provided with hybrid telepsychiatry (team-based practice with social worker traveling to the home with electronic tablet for connection with psychiatrist). The intervention resulted in detecting unrecognized depression and complex trauma. The treatment plan included adding an antidepressant and therapy plan, eliminating one psychiatric medication, and reducing dosage of pain medication. The outcomes were improved function and quality of life. The patient and caregiver were both highly satisfied with the services. This hybrid telepsychiatry is a reasonable option for homebound elderly patients living in urban areas and less expensive than nursing home admission.

Intervention to reduce inpatient psychiatric admission in a metropolitan city.

When psychiatric hospitalization is over-used, it represents a financial drain and failure of care. We evaluated implementation and cessation of transporting people medically certified for psychiatric hospitalization to a central psychiatric emergency service for management and re-evaluation of hospitalization need. After implementation, the hospitalization rate declined 89% for 346 transported patients; only four of the nonhospitalized patients presented in crisis again in the next 30 days. Following cessation, the hospitalization rate jumped 59% compared to the preceding year. Costs declined 78.7% per diverted patient. The findings indicate that it is possible to reduce hospitalization and costs, and maintain quality care.

Economic grand rounds: experience with mandated use of generic medications for patients covered by the mental health safety net.

Reducing pharmacy costs without increasing adverse outcomes would relieve some pressure on mental health budgets. This column describes the experience of a publicly funded provider network in a Michigan county that mandated generic use of psychotropic medications to address financial challenges. The percentage of brand-name medications and cost per prescription declined with the policy change, resulting in lower total pharmacy expenditures. No increase was noted in prescriptions per patient or psychiatric hospitalizations. Changes were sustained after the initial implementation period. Mandating generic use may be feasible as a tool for constraining pharmacy costs in mental health budgets.

Evoked potential correlates of post-traumatic stress disorder in refugees with history of exposure to torture.

The presence and magnitude of information processing deviations associated with Post-Traumatic Stress Disorder (PTSD) are far from being well-characterized. In this study we assessed the auditory and visually evoked cerebral responses in a group of Iraqi refugees who were exposed to torture and developed PTSD (N = 20), Iraqi refugees who had been exposed to similar trauma but did not develop PTSD (N = 20), and non-traumatized controls matched for age, gender, and ethnicity (N = 20). We utilized two paired-stimulus paradigms in auditory and visual sensory modalities, respectively. We found significantly smaller amplitudes of both the auditory P50 and the visual N75 responses in PTSD patients compared to controls, reflecting decreased response to simple sensory input during a relatively early phase of information processing (interval 50-75 ms post stimulus). In addition, deficient suppression of the P50/N75 response to repeating stimuli at this early stage in both modalities is indicative of difficulty in filtering out irrelevant sensory input. Among associations between electrophysiological and clinical measures, a significant positive correlation was found between dissociation score and P50 S1 amplitudes (p = 0.024), as well as stronger auditory P50 gating correlated with higher quality-of-life index scores (p = 0.013). In addition, smaller amplitudes of N150 visual evoked response to S1 showed a significant association with higher avoidance scores (p = 0.015). The results of this study highlight the importance of early automatic auditory and visual evoked responses in probing the information processing and neural mechanisms underlying symptomatology in PTSD.

Event-related potential studies of post-traumatic stress disorder: a critical review and synthesis.

Despite the sparseness of the currently available data, there is accumulating evidence of information processing impairment in post-traumatic stress disorder (PTSD). Studies of event-related potentials (ERPs) are the main tool in real time examination of information processing. In this paper, we sought to critically review the ERP evidence of information processing abnormalities in patients with PTSD. We also examined the evidence supporting the existence of a relationship between ERP abnormalities and symptom profiles or severity in PTSD patients. An extensive Medline search was performed. Keywords included PTSD or post-traumatic stress disorder, electrophysiology or EEG, electrophysiology, P50, P100, N100, P2, P200, P3, P300, sensory gating, CNV (contingent negative variation) and MMN (mismatch negativity). We limited the review to ERP adult human studies with control groups which were reported in the English language. After applying our inclusion-exclusion review criteria, 36 studies were included. Subjects exposed to wide ranges of military and civilian traumas were studied in these reports. Presented stimuli were both auditory and visual. The most widely studied components included P300, P50 gating, N100 and P200. Most of the studies reported increased P300 response to trauma-related stimuli in PTSD patients. A smaller group of studies reported dampening of responses or no change in responses to trauma-related and/or unrelated stimuli. P50 studies were strongly suggestive of impaired gating in patients with PTSD. In conclusion, the majority of reports support evidence of information processing abnormalities in patients with PTSD diagnosis. The predominance of evidence suggests presence of mid-latency and late ERP components differences in PTSD patients in comparison to healthy controls. Heterogeneity of assessment methods used contributes to difficulties in reaching firm conclusions regarding the nature of these differences. We suggest that future ERP-PTSD studies utilize standardized assessment scales that provide detailed information regarding the symptom clusters and the degree of symptom severity. This would allow assessment of electrophysiological indices-clinical symptoms relationships. Based on the available data, we suggest that ERP abnormalities in PTSD are possibly affected by the level of illness severity. If supported by future research, ERP studies may be used for both initial assessment and treatment follow-up.

Lunar phase cycle and psychiatric hospital emergency visits, inpatient admissions and aggressive behavior.

INTRODUCTION: We examined the correlation between lunar cycles and the number of psychiatric emergency visits, patients' gender, aggressive behavior, need for inpatient admission, legal referral and need for involuntary chemical restraint in a period of one calendar year. METHOD: Charts of all psychiatric emergency room patients were reviewed retrospectively. Arabic calendar lunar months were divided based on three different models: Two 15 days sections, three 10 days, and six 5 days parts in the third model. RESULTS: 5431 patients were seen in the psychiatric emergency service (PES) during a one year period. We did not find a relationship between the visit time (day or night), gender, and legal referral in relation to moon cycles. A higher number of visits during full moon period which was not statistically significant (P>0.05) was found. Highest frequency of inpatient admissions was discovered in the first and last parts of the three part model and in the first and last segments of the six part model followed by second and fifth parts (P-values: 0.000). CONCLUSION: This study revealed a slight increase in number of visits to psychiatric emergency room during full moon periods. In addition a highly significant increase in the severity of illness and aggressive behaviors and agitation in the beginning and end of the moon cycles were noticed. Some of the underlying possible causes such as changes in intra/extracellular fluids, neural and endocrine cell functions, hemodynamic and biological responses and changes in social dynamics and support are discussed.

Case-control study of frequent visitors to an urban psychiatric emergency service.

OBJECTIVE: The purpose of this study was to identify risk factors for people who use psychiatric emergency services repeatedly and to estimate their financial charges. METHODS: The authors used interviews and chart reviews to compare 74 patients who had six or more visits to an urban psychiatric emergency service in the 12 months before an index visit with 74 patients who had five or fewer visits. Multivariate logistic regression was used to identify independent risk factors. RESULTS: Independent risk factors for frequent visitors were self-reported hospitalization in the past 12 months, need for medications as the self-reported reason for seeking care, being homeless or living in an institution, and not giving the name of a friend or family member for interview. The level of burden for support of persons who were interviewed was low and did not differ between frequent and infrequent visitors. Compared with infrequent visitors, frequent visitors had greater utilization of inpatient and outpatient behavioral health services, general emergency services, and crisis residential services in the 12 months before the index visit and greater utilization of general emergency services and psychiatric emergency services in the three months after the index visit. Frequent visitors' median financial charge for those services was 16,200 US dollars greater (5.9 times greater) than that of infrequent visitors. CONCLUSIONS: Frequent visitors represent resource-poor mentally ill persons who have high levels of utilization of health care facilities besides psychiatric emergency services. Possible clinical interventions for these patients include focused medication reviews.

Frequent visitors to psychiatric emergency services: staff attitudes and temporal patterns.

Providing quality psychiatric emergency services is becoming more difficult as utilization rates soar, especially by individuals who are frequent visitors. To address this issue, a staff survey and analysis of admission patterns were conducted. Staff were more likely to believe that frequent visitors sought care because they had difficulty accessing alternative services, had basic needs unmet, were substance abusers, wanted inpatient admission, and were noncompliant with treatment plans. The 1999 temporal admission pattern documented that frequent visitors' admissions were higher during the first week of the month and inclement weather. Surprisingly, the infrequent visitors' admissions also were higher during the first week of the month. Together, these findings suggest that, in this urban location, frequent visitors are disadvantaged individuals lacking support and alternative treatment settings who use psychiatric emergency services to meet basic needs.