Table of Contents

Basic and Laboratory Science Initiatives

The basic science initiatives of the VISN 3 MIRECC revolve around understanding the neuropsychological and neurobiological factors that contribute to serious mental illness (SMI) in veterans and in the population as a whole. Neuropsychological factors are studied with formal, systematic, and detailed assessments of veterans with SMI at regular intervals, while the centerpiece of the study of neurobiological factors is a well-established Brain Bank. Brain tissues donated to the Brain Bank are fully characterized neuropathologically and are distributed to dozens of VISN 3 MIRECC and external laboratories performing state-of-the-art neurobiological studies. T he combination of antemortem neuropsychological assessments and postmortem neurobiological studies provides the unprecedented opportunity to relate neuropsychological deficits to their potential neurobiological substrates.

• Mental health related publications since MIRECC award: 50
• Continued characterization of glutamine-glutamate-GABA pathway in schizophrenia
• Continued characterization of mRNA and protein expression of ionotropic glutamate receptors and associated transporters and intracellular trafficking molecules in schizophrenia
• Continued study of genome-wide gene expression by microarray to supplement the seventeen brain regions already studied with additional cases and in additional regions
• Continued study of glutamate-related gene expression in anatomically defined nuclei within the thalamus in schizophrenia
• Studies to characterize gene expression in laser assisted microdissections of identified cells in the cortex, hippocampus and thalamus in schizophrenia
• Studies to expand on our previously reported findings of myelin-associated gene expression deficits in multiple brain regions in schizophrenia
• Studies to characterize the relationship between myelin-associated mRNA and protein expression in schizophrenia
• Continued exploration of myelin-associated gene expression in grey vs. white matter throughout the course of human development from less than one through 105 years of age (studies in collaboration with Dr. Joel Kleinman)
• Continued efforts to build on recent success to increase autopsy rates at the Bronx VAMC
• Continued efforts to build on recent success to obtain brain tissue donations from Suffolk County ME
• Continued development of Brain Bank and associated neuropsychological data warehouse

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The Assessment and Brain Banking Core

The VISN 3 MIRECC Brain Bank is part of a larger Mental Illness and Alzheimer's Disease Brain Bank directed by V. Haroutunian, Ph.D., and is a joint initiative of the Bronx VA Medical Center Psychiatry Service and the Mount Sinai Department of Psychiatry. The MIRECC component of the Brain Bank accepts brain tissue donations from veterans receiving care at the NJ Veterans Health Care Network, VA Hudson Valley Health Care System, and the Northport VAMC. The Brain Bank is supported by multiple grants, including the VISN-3 MIRECC, an NIMH sponsored Mental Illness Clinical Research Center, the Mount Sinai School of Medicine Alzheimer's Disease Research Center, and a Program Project Grant to Study Early Dementia. It currently holds brain tissue specimens from over 1180 cases, many of which are generously donated by families of patients who have participated in neuropsychological assessment and treatment studies. After detailed neuropathological examination, brain tissue specimens are distributed to research laboratories within the Bronx VAMC, the Mount Sinai School of Medicine, and over 20 different collaborating laboratories within the United States and abroad. This Brain Bank directly supports the Molecular biology, Neurochemistry and Neuroanatomy basic science projects of the VISN-3 MIRECC.

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Clinical and Neuropsychological Assessments of Severely Mentally Ill Veterans

Philip Harvey, PhD

The objective of the VISN3 Assessment Program is to perform state-of-the-art detailed clinical and neuropsychological assessments of SMI-veterans and to make these results available to health care professionals. The Assessment Battery consists of diagnostic reassessment, Assessment of Negative and Positive Symptoms (PANSS), Assessment of Cognition and Function (MMSE, CDR, CERAD Cognitive Battery, supplemented with additional assessments), the Social Adaptive Functioning Evaluation (SAFE) Scale or the Specific Levels of Functioning Scale (SLOF) depending on the residential status of the veteran. In addition to providing support for enhanced clinical care of veterans, this project directly supports the Neurochemistry and Neuroanatomy basic science projects of the VISN-3 MIRECC.

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Clinical Assessments in the Chronic Psychosis Project

Philip Harvey, PhD; Harry Haroutunian, PhD

This clinical initiative focuses on diagnostic re-evaluation, symptomatic assessment, cognitive evaluation, and functional appraisal. To date, over 900 assessments and 225 re-evaluations have been conducted at four VISN3 sites, and every VISN inpatient over age 55 has been seen. Recently, the project has received additional federal funding to expand the efforts into longitudinal assessment of functional skills in older community dwelling SMI patients. Expanding on the previous discharge monitoring studies, this five-year project will examine the course of cognitive and functional status, with the goal of identifying points of intervention.

The results of the joint MIRECC-Mt. Sinai study on aging in schizophrenia have been published in numerous refereed scientific journals and have been characterized by reviewers as essentially defining the field of cognitive and functional change in older patients with schizophrenia. These studies have both compared the characteristics of VA and public sector patients, as well as examining the course of functional status in large samples of patients including veterans.

1. Course of functional decline in older patients with schizophrenia: We have shown that older institutionalized patients have an individual risk for cognitive and functional decline that approximates 18% per year. This risk is not simply an artifact of physical illness; in fact functional impairment increases risk for later functional decline. This risk of worsening was age-associatedand did not resemble the decline seen in Alzheimer’s disease. In patients who experience decline in their functional status, cognitive decline is a substantial predictor of this worsening. Further, the severity of functional decline is largely predicted by the severity of cognitive decline. Cognitive decline appears to be worse in patients who experience continuous treatment refractory psychosis, in that the cross-sectional relationship between psychotic symptoms and cognitive functioning is essentially zero, while the random-effects regression correlation between the course of cognitive functioning and the course of cognitive decline is quite substantial.
2. Aging-related changes in cognitive functioning in treatment responsive and treatment refractory samples: Data from this study again are consistent with the idea that the experience of chronic psychotic symptoms may lead to cognitive decline. Previous data have suggested that even ambulatory patients may experience decline in executive tasks and in information processing capacity. The Boston Naming Test, the Animal Naming Test, Word List Learning, Letter-Number Sequencing, and the Constructional Praxis Test were used to assess differences between a normative sample of older healthy controls, a demographically similar sample of older healthy controls, ambulatory Schizophrenia patients aged 50 to 80, and an institutionalized and treatment refractory sample of Schizophrenic patients aged 50 to 80. As can be seen in the next three slides, tasks that required verbal skills and episodic memory manifested significant age-associated declines in refractory patients only, with nonrefractory patients showing no age associated differences. Tests of executive functioning and working memory, however, worsened in both refractory and nonrefractory patients. These data suggest that aging in chronic schizophrenia selectively impacts on high-capacity tasks, while the experience of treatment-refractory psychosis has broad ranging effects.
3. The impact of substance abuse: Substance abuse is very common in Schizophrenia, with approximately 50 percent of patients showing at least episodic abuse. Though this is less of an issue for institutionalized populations, even treatment refractory patients often live in the community now. This study compared VA outpatients with schizophrenia who were recent alcohol abusers to nonabusers. Data from this assessment suggest that dually diagnosed patients experience more overall cognitive decline with aging than do patients with Schizophrenia alone. This impairment was particularly salient in episodic memory performance. Finally, this impairment in cognitive performance was directly functionally relevant, as the differences in functional outcome between the substance abusing and nonabusing patients with schizophrenia was completely accounted for by cognitive changes.

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Clinical Genetics Research

Jeremy Silverman, PhD; Larry Siever, MD

Schizophrenia is strongly familial, but both genetic and non-genetic factors seem to be involved in its development.The specific genetic risk factors remain unknown. The first Molecular Genetics of Schizophrenia MGS-1 project, an affected sibling pair study, was completed in August 2003. MGS-II, a genetic association study, began in September 2003 and will run through August 2007 in ten collaborating centers. This NIMH-sponsored study is projected to employ 4,500 Schizophrenic patients and 4,500 controls in an effort to identify one or more Schizophrenia susceptibility genes. A gene bank for Schizophrenia genetic association studies is established and utilized at Rutgers University.

Research is underway to identify the link between certain characteristics called endophenotypes (such as eye movements and verbal memory) in families and the development of schizophrenia. Seven centers are collaborating to examine this relationship between genetic differences and potential endophenotypes. Six endophenotypes in patients with schizophrenia and in their family members were selected for measurement. Analyses will determine whether these endophenotypes reflect the influence of a single common gene or multiple genes.

Key measures of neurophysiological deficits include P50 event related suppression, prepulse inhibition of acoustic startle response, and the antisaccade task for eye movements. Neurocognitive deficits are revealed by poor performance on the Continuous Performance Test (CPT), the California Verbal Learning Test (CVLT) to assess verbal memory, and the Letter Number Sequencing subtest of the WAIS III to measure working memory. Each of these deficits has also been demonstrated in clinically unaffected relatives of schizophrenic patients, which is evidence that these deficits may reflect part of the heritable risk for the illness. Goals of the study include the establishment of a neurocognitive/psychophysiological laboratory for genetic/family studies in Schizophrenia and other disorders; recruitment of fifteen Schizophrenic proband families a year for five years; establishment of a gene bank for 420 pedigrees; characterization of the complex relations among the major endophenotypes in the families; and implementation of a genome scan for Schizophrenia and endophenotypic traits.

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Neuroimaging Studies

Understanding of the neuropathology of schizophrenia has been advanced by numerous magnetic resonance imaging (MRI) studies over the past decade, which confirms the presence of structural brain abnormalities in schizophrenia, including volume alterations of the ventricles, frontal lobe, medial temporal lobe, superior temporal gyrus, inferior parietal lobe and subcortical brain regions. Conte Center (Mount Sinai School of Medicine) affiliated studies on Diffusion Tensor Imaging (DTI), Magnetization Transfer Imaging (MTI), and Proton Magnetic Resonance Spectroscopy (MRS) are underway to assess cognitive components and functional outcomes of Chronic Schizophrenics. The studies involve complete cognitive batteries, symptomological assessments, and investigation of brain white matter structures and neurochemicals.

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fMRI of VisuoSpatial Working Memory in Schizotypal Personality Disorder

Harold Koenigsberg, MD, et al

As with Schizophrenic patients, the visuo-spatial working memory of individuals with Schizotypal Personality Disorder (SPD) is impaired. Visuo-spatial working memory (VSWM) affects a wider range of Schizophrenic patients than does impairment in verbal working memory, and connects to extensive non-human primate work including single-cell recordings. This study was developed with the hypothesis that SPD patients will activate regions in the frontal part of the brain normally used in working memory (called regions BA9/46) less strongly than will healthy volunteers, and that SPD individuals will activate a different region at the very front of the brain (the frontal pole; called region BA10) more strongly than will healthy volunteers, while performing the VSWM task. Preliminary data reveal that SPD patients and healthy controls (HC) show increased activation during the memory maintenance period compared to the control condition. However, HC's exhibit greater activation in right BA9/46 than do SPD patients, while SPD patients show greater activation in right BA10 than do HC's. In addition, our findings on ventral prefrontal cortex activation, activation in premotor areas, and parietal cortex activation replicate findings from published literature on spatial memory. Future directions include a comparison of Schizophrenic, SPD, and HC subjects in the same study, employment of a larger sample size, and examination of the effect of working memory load.

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A Thalamocentric Approach to the Neuroanatomy of Schizophrenia: A Quantitative Study in Immunocytochemically Identified Thalamocortical Projection Neurons

William Byne, MD, PhD

Schizophrenia is a psychiatric disorder characterized by functional and structural abnormalities in multiple brain regions, all of which communicate with the part of the brain called the thalamus. The thalamus can, therefore, be considered as a communication hub of the brain. Pathology in a given brain region may induce pathology in other regions of the brain with which it communicates. Thus the abnormalities in multiple brain regions in schizophrenia may be causally related by virtue of their communication with the thalamus.

We have, therefore, investigated the thalamus for pathology associated with schizophrenia. Our overarching hypothesis is that pathology will be found in those regions of the thalamus that communicate with other brain regions which are known to be abnormal in schizophrenia. We have identified two large regions (nuclei) of the thalamus that are characterized by decreased volume and cell number in schizophrenia. These nuclei are the mediodorsal nucleus and pulvinar. The present application focuses on the pulvinar, which comprises five separate divisions, each of which has a different pattern of communication (connections) with other brain regions. Identifying exactly which of these divisions are affected in schizophrenia is therefore essential to understanding how the disorder alters brain circuitry. The study employs autopsied human thalami obtained from the Brain Bank, and aims to examine approximately thirty-six specimens (eighteen from schizophrenics and eighteen from nonschizophrenic comparisons).

To date there has been no satisfactory unifying hypothesis to explain the multiple functional and neuroanatomical abnormalities associated with schizophrenia. We have adopted an approach to neuroanatomical schizophrenia research which is premised on the unifying hypothesis that some of the multiple brain abnormalities associated with this disorder are etiologically related by virtue of the communication of the affected brain regions with the thalamus. Rather than resulting from multiple lesions independently affecting various functional circuits, multiple functional deficits might be better explained by a lesion in the thalamus where the relevant circuits converge. Because pathology in one brain region may induce pathology in other brain regions with which it communicates, thalamic pathology may also hold a key to understanding why multiple brain regions exhibit schizophrenia-associated structural, cellular, and neuromolecular anomalies.

We have demonstrated a schizophrenia-associated loss of volume in the mediodorsal nucleus and in the pulvinar of the thalamus in both postmortem histological and in vivo neuroimaging studies. Our large scale (N=101) MRI study included neuroleptic naive subjects ranging in age from 18-73 and suggested that the volume loss is independent of neuroleptic exposure and does not progress with age. Our postmortem studies have demonstrated neuronal loss in both of these thalamic nuclei and a loss of dendritic material in two of their prefrontal cortical fields. Both of these thalamic nuclei are comprised of multiple subdivisions which have unique sets of efferent and afferent projections. Understanding which subdivions are affected is, therefore, crucial to understanding how schizophrenia may impair neural circuitry. Current work employs well-characterized material from the Mount Sinai/Bronx VA Schizophrenia Brain Bank and is aimed at determining precisely which cell types (e.g., glia, projection neurons, interneurons) and which subdivisions of the mediodorsal nucleus and pulvinar are affected in schizophrenia. We are also beginning to examine the thalamus for abnormalities associated with major depression and bipolar disorder.

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Clinical Intervention/Pharmacotherapy Core

The goal of the Pharmacotherapy Unit is to create an infrastructure and, subsequently, conduct novel psychopharmacologic interventions for improving the functional outcome of patients with schizophrenia.

Effects of Dialectical Behavioral Therapy and Escitalopram on Impulsive Aggression, Affective Instability, and Cognitive Processing in Borderline Personality Disorder

Marianne Goodman, MD

This study investigates the effects of pharmacologic and psychotherapy treatment on three core biological factors that predispose an individual to borderline personality disorder (BPD): impulsive aggression, lability of affect, and cognitive processing. Forty-two subjects with BPD are currently receiving dialectical behavioral therapy (DBT), and were randomized to six months of treatment with either escitalopram or placebo. DBT is an empirically validated treatment modality for this population. Treatment effects on impulsivity, aggression, cognitive processing, and affective instability are being measured by a variety of modalities including assessment thorough clinical/self ratings, analogue laboratory tasks, and psychophysiologic measures. We are unaware of any study on BPD to date that includes biological outcome measures for DBT treatment or compares efficacy of combined treatment strategies.

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Clinical Trials: Clozapine/Pimozide

Joseph Friedman, MD

Despite its utility in the treatment of refractory psychosis, many patients’ symptoms do not fully resolve with Clozapine monotherapy. Thus, numerous patients are prescribed combination antipsychotic therapy, despite a lack of research evidence base. Unique among first-generation (“typical”) antipsychotic agents, Pimozide does not cause an upregulation of post-synaptic D2 receptors (Clozapine is the only other agent with this property). An open-label study of the Clozapine/Pimozide combination demonstrated improvements in psychotic symptoms and in need for hospitalization in the Pimozide group (put reference here from Pim. Protocol). The current study explores the combination’s effect on Brief Psychiatric Rating Scale (BPRS) totals in Schizophrenic and Schizoaffective patients.

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Clinical Trials: Cognitive Enhancement

Joseph Friedman, MD

Cognitive dysfunction is a core feature of schizophrenic syndrome, and correlates highly with occupational, social, other functional outcomes. Unfortunately, antipsychotic medication alone does not significantly improve this symptom cluster. Two studies are underway to analyze the effects of augmenting atypical treatment with Guanfacine or Atomoxetine to reduce cognitive dysfunction in Schizophrenic and Schizoaffective patients.

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"Impact of Clozapine"???

Bruce Levine, MD

The purpose of this project is to determine the impact of Clozapine on the symptoms and recovery of the SMI outpatients in VISN 3. SMI outpatients eligible for a switch to Clozapine include all patients who have been tried on two antipsychotics for an adequate dose and time. These antipsychotics must be one second generation antipsychotic plus one other antipsychotic, either first or second generation. All patients currently taking more than one antipsychotic are also considered eligible. Rehospitalization within same year of discharge, continued impairment from positive or negative symptoms, high utilization of emergency services without rehospitalization, high utilization of ICM times, noncompliance because of side effects of other medications, and tardive dyskinesia are the clinical determinants that the patient is not doing well on his/her current regimen.

We will focus on the effectiveness of Clozapine among treatment refractory outpatients as compared to patients on multiple antipsychotics. These patients will then be followed for community tenure, rehospitalizations, use of emergency services, deaths, other adverse medical events, level of restriction of living situation, sheltered work, competitive employment, and aggressive or suicidal incidents. Outcomes will then be compared. We hypothesize that Clozapine will decrease adverse advents and increase the indicators of symptom amelioration and recovery.

Outcomes will be measured initially by patients’ medication regimens. Patients who remain on Clozapine alone until the end of the study will be viewed as treatment successes. Likewise, patients in the stay group who remain on their original regimens will indicate a positive treatment outcome. Measures of outcome will involve administrative data such as rehospitalizations, use of emergency services, deaths and adverse medical events, readmissions to other non-community treatment settings, and measures of psychiatric symptomatology including the Positive and Negative Symptom Scale (PANSS, a measure of functioning and quality of life) and the Abnormal Involuntary Movement Scale (AIMS). We will also be looking at the rate of switch to Clozapine in the treatment as usual group compared to historical rates.

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Clinical Intervention/Psychosocial Unit

The clinical intervention/psychosocial unit is designed to understand the impact of novel or underutilized psychosocial interventions on SMI veterans’ outcome in the community. Below are examples of current research and therapeutic programs.

Dialectical Behavioral Therapy and Family Skills Training for Patients with Borderline Personality Disorder and their Family Members

Marianne Goodman, MD, et al.

Dialectical Behavioral therapy (DBT) is a manualized cognitive behavioral treatment approach developed to treat chronically suicidal individuals, many of whom met criteria for Borderline Personality Disorder (BPD). The approach combines behavioral interventions including skills training, exposure, problem solving with cognitive techniques of mindfulness, and stresses the importance of client-therapist connection. The DBT approach has also been successfully adapted to inpatient settings, criminal justice settings, outpatient populations of BPD substance abusers, depressed and suicidal adolescents with BPD or BPD traits, and binge-eating disordered individuals.

Despite the pronounced difficulties in interpersonal relationships inherent in BPD, minimal attention has been paid to couples and family treatment in the literature. We are currently treating subjects with Borderline Personality Disorder and their family memberswith a seven-session course of familyDialectical Behavioral Therapy to examine the impact of family DBTon measures of mood and emotion, aggression, family function, intrafamily conflict tactics and violence, relationship quality and adjustment, and communication patterns. Preliminary data will be available after January 2005.

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Maintaining Independence and Sobriety through Systems Integration, Outreach, and Networking: The MISSION Program

David Smelson, PsyD, et al.

The purpose of the MISSION program is to promote the successful integration of homeless, dually diagnosed veterans into their communities through a comprehensive system of care that provides integrated mental health and substance abuse treatment, case management, and supported employment. The program will also focus on improving long-term service system effectiveness by enhancing interagency communication and service coordination. This is a five-year CSAT, $2M grant, which received the highest rank among all applicants this year. Goals of the program include reduction of number of homeless days and improvement of community tenure; reduction of re-hospitalizations; enhancement of dual recovery by reducing addiction slips/relapses and psychiatric symptoms/relapses; and increasing the number of days employed and the wages earned. Treatment initiatives consist of Integrated Dual Disorders Treatment, Supported Employment, Critical Time Intervention Case Management, Peer Support, and Community Network Enhancement (Systems Broker).

MIRECC solicited proposals via the MHEB for new peer supported case management projects after the previous MIRECC-supported initiative at TORCH was completed. We have funded one proposal at NY Harbor, “MentorshiThursday, August 9, 2007 7:49 PMng the possibility of funding a second study.

This project consists of a weekly mentorship group and a weekly individual mentorship pair contact. Ten veterans (five mentors and five mentees) will participate in MSAT for eight weeks, and twenty veterans will be randomized to either MSAT or TAU.

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Time Limited Case Management for Severe Mental Illness and Substance Abuse Disorders (TLC)

David Smelson, PsyD; Miklos Losonczy, MD, PhD

The TLC model is a brief, intensive case management approach, providing a community linkage intervention that assists highly recidivist individuals with a persistent mental illness and co-occurring substance abuse (MICA) disorder with the transition from Acute Psychiatry to an outpatient MICA program in a Day Treatment Center. The treatment includes a modified form of Dual Recovery Therapy, which is a blending of tradi tional addiction treatment therapies (relapse prevention, motivational enhancement therapy, and 12-step Facilitation) with mental health approaches (cognitive-behavioral therapy and social skills training that varies according to the mental health problems) specifically designed to meet the unique needs of the dually diagnosed veteran. The program also incorporates elements of the Critical Time Intervention (CTI) Case Management Approach, which was originally developed to assist the homeless mentally ill in the engagement to the community. We specifically selected CTI as the case management approach because it incorporates effective discharge planning strategies, which are critical for the transition of our veterans from Acute Psychiatry to the Day Treatment Center. Both approaches have accompanying treatment manuals that we modified for an eight-week format, which will assist in the dissemination to other facilities.

The outcomes to date have far surpassed our expectations, with dramatic individual improvements in a population that heretofore appeared to resist all efforts to help them. In addition, we believe that the TLC approach is both innovative and incorporates components of other best practices. The pilot study examined the integrated DRT and CTI approaches using a quasi-experimental design that included a group of mentally ill substance-abusing veterans who received the new TLC transitional service (N= 33), compared to a group of veterans who were offered the service, but refused it, and were subsequently discharged as usual (N= 29). Initial eight week post-treatment outcomes suggest that the individuals who received the service had significantly better attendance at the initial outpatient screening appointment (83% versus 55%, P= 0.02 ), were more likely to complete the second week of treatment (80% versus 38% P=0.001) , had better overall attendance in the Day Treatment Center (15.5 versus .72 days P=.001) and were less likely to be lost to follow-up at eight weeks (18% versus 76.9% P=.0001) compared to those who were discharged as usual without the service. Furthermore, the individuals who received the TLC service also seemed to have better medication compliance as indicated by the greater pharmacy prescription pick-ups ( 93% versus 79%, P=0.11).

The six month post treatment outcomes showed a significant reduction in psychiatric rehospitalization days among the individuals who received the TLC service (13.1 versus 33 P=.05). This reduction in hospital days was particularly striking considering that the six-month pretreatment data indicated that those in the TLC group had more inpatient psychiatric treatment days ( 40.1 versus 30.5, P=.24 ).

In terms of symptom severity, the individuals in the TLC group also showed a significant reduction in symptom severity on the BASIS 32 Relation to Self and Others (P=.006), Depression and Anxiety (P=.006), Daily Living/Role Functioning (.001) and Impulsive/Addictive (P=.02) subscale scores. Functional outcome assessments also indicated that the TLC group had greater improvement on the Clinical Global Improvement scale (3.9 versus 4.3 P= .07) and higher functioning on the Global Assessment in Functioning (56.2 versus 46.2 P=0001). These six-month outcomes are particularly exciting and suggest that the TLC intervention had robust treatment effects well beyond the eight weeks of treatment. It is also important to note that one individual in the TLC group also received Mental Health Intensive Case Management following the eight-week TLC intervention. The Mental Health Intensive Case Management was discontinued after six months because the individual was attending the Day Treatment Center regularly and no longer needed the intensive community outreach. No other individuals in either group received any other form of case management or additional outpatient treatment services besides the TLC and Day Treatment. Interestingly, as this intervention has become known throughout the veteran population, the percent of patients declining the intervention has also declined.

• 50% ECA Study (Regier et al., 1991)
• 80% in Community Mental Health Setting (Ziedonis et al., 1996)
• 25% VA National Data Sets (Blow, 1997; Rosenheck, 1998)

• Increased symptoms
• More cognitive deficits
• More suicide
• More assaults
• More costly service utilization

• Treatment completion in MICA: 15%-30% (Rehav et al., 1995; Bemmet et al, 1995)
• Difficulty transitioning to lower levels of care: 9% successfully transitioned from acute to day treatment (Bennet et al., 2001)
• VA-New Jersey: 50% fail to attend initial DTC appointment; 70% poor treatment engagement

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