H. Ryan Wagner

A comparison of automated segmentation and manual tracing for quantifying hippocampal and amygdala volumes

Large databases of high-resolution structural MR images are being assembled to quantitatively examine the relationships between brain anatomy, disease progression, treatment regimens, and genetic influences upon brain structure. Quantifying brain structures in such large databases cannot be practically accomplished by expert neuroanatomists using hand-tracing. Rather, this research will depend upon automated methods that reliably and accurately segment and quantify dozens of brain regions. At present, there is little guidance available to help clinical research groups in choosing such tools. Thus, our goal was to compare the performance of two popular and fully automated tools, FSL/FIRST and FreeSurfer, to expert hand tracing in the measurement of the hippocampus and amygdala. Volumes derived from each automated measurement were compared to hand tracing for percent volume overlap, percent volume difference, across-sample correlation, and 3-D group-level shape analysis. In addition, sample size estimates for conducting between-group studies were computed for a range of effect sizes. Compared to hand tracing, hippocampal measurements with FreeSurfer exhibited greater volume overlap, smaller volume difference, and higher correlation than FIRST, and sample size estimates with FreeSurfer were closer to hand tracing. Amygdala measurement with FreeSurfer was also more highly correlated to hand tracing than FIRST, but exhibited a greater volume difference than FIRST. Both techniques had comparable volume overlap and similar sample size estimates. Compared to hand tracing, a 3-D shape analysis of the hippocampus showed FreeSurfer was more accurate than FIRST, particularly in the head and tail. However, FIRST more accurately represented the amygdala shape than FreeSurfer, which inflated its anterior and posterior surfaces.

The Social–Environmental Context of Violent Behavior in Persons Treated for Severe Mental Illness

OBJECTIVES This study examined the prevalence and correlates of violent behavior by individuals with severe mental illness. METHODS Participants (N = 802) were adults with psychotic or major mood disorders receiving inpatient or outpatient services in public mental health systems in 4 states. RESULTS The 1-year prevalence of serious assaultive behavior was 13%. Three variables-past violent victimization, violence in the surrounding environment, and substance abuse-showed a cumulative association with risk of violent behavior. CONCLUSIONS Violence among individuals with severe mental illness is related to multiple variables with compounded effects over the life span. Interventions to reduce the risk of violence need to be targeted to specific subgroups with different clusters of problems related to violent behavior.

Comparison of antipsychotic medication effects on reducing violence in people with schizophrenia

BACKGROUND Violence is an uncommon but significant problem associated with schizophrenia. AIMS To compare antipsychotic medications in reducing violence among patients with schizophrenia over 6 months, identify prospective predictors of violence and examine the impact of medication adherence on reduced violence. METHOD Participants (n=1445) were randomly assigned to double-blinded treatment with one of five antipsychotic medications. Analyses are presented for the intention-to-treat sample and for patients completing 6 months on assigned medication. RESULTS Violence declined from 16% to 9% in the retained sample and from 19% to 14% in the intention-to-treat sample. No difference by medication group was found, except that perphenazine showed greater violence reduction than quetiapine in the retained sample. Medication adherence reduced violence, but not in patients with a history of childhood antisocial conduct. Prospective predictors of violence included childhood conduct problems, substance use, victimisation, economic deprivation and living situation. Negative psychotic symptoms predicted lower violence. CONCLUSIONS Newer antipsychotics did not reduce violence more than perphenazine. Effective antipsychotics are needed, but may not reduce violence unrelated to acute psychopathology.

The prevalence of posttraumatic stress disorder in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans: A meta-analysis

Literature on posttraumatic stress disorder (PTSD) prevalence among Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) veterans report estimates ranging from 1.4% to 60%. A more precise estimate is necessary for projecting healthcare needs and informing public policy. This meta-analysis examined 33 studies published between 2007 and 2013 involving 4,945,897 OEF/OIF veterans, and PTSD prevalence was estimated at 23%. Publication year and percentage of Caucasian participants and formerly active duty participants explained significant variability in prevalence across studies. PTSD remains a concern for a substantial percentage of OEF/OIF veterans. To date, most studies have estimated prevalence among OEF/OIF veterans using VA medical chart review. Thus, results generalize primarily to the prevalence of PTSD in medical records of OEF/OIF veterans who use VA services. Additional research is needed with randomly selected, representative samples administered diagnostic interviews. Significant financial and mental health resources are needed to promote recovery from PTSD.

Amygdala Volume Changes in Posttraumatic Stress Disorder in a Large Case-Controlled Veterans Group

CONTEXT Smaller hippocampal volumes are well established in posttraumatic stress disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have produced equivocal results. OBJECTIVE To assess a large cohort of recent military veterans with PTSD and trauma-exposed control subjects, with sufficient power to perform a definitive assessment of the effect of PTSD on volumetric changes in the amygdala and hippocampus and of the contribution of illness duration, trauma load, and depressive symptoms. DESIGN Case-controlled design with structural magnetic resonance imaging and clinical diagnostic assessments. We controlled statistically for the important potential confounds of alcohol use, depression, and medication use. SETTING Durham Veterans Affairs Medical Center, which is located in proximity to major military bases. PATIENTS Ambulatory patients (n = 200) recruited from a registry of military service members and veterans serving after September 11, 2001, including a group with current PTSD (n = 99) and a trauma-exposed comparison group without PTSD (n = 101). MAIN OUTCOME MEASURE Amygdala and hippocampal volumes computed from automated segmentation of high-resolution structural 3-T magnetic resonance imaging. RESULTS Smaller volume was demonstrated in the PTSD group compared with the non-PTSD group for the left amygdala (P = .002), right amygdala (P = .01), and left hippocampus (P = .02) but not for the right hippocampus (P = .25). Amygdala volumes were not associated with PTSD chronicity, trauma load, or severity of depressive symptoms. CONCLUSIONS These results provide clear evidence of an association between a smaller amygdala volume and PTSD. The lack of correlation between trauma load or illness chronicity and amygdala volume suggests that a smaller amygdala represents a vulnerability to developing PTSD or the lack of a dose-response relationship with amygdala volume. Our results may trigger a renewed impetus for investigating structural differences in the amygdala, its genetic determinants, its environmental modulators, and the possibility that it reflects an intrinsic vulnerability to PTSD.

Substance use in persons with schizophrenia: Baseline prevalence and correlates from the NIMH CATIE study

This study examined baseline correlates of substance use in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness project. Approximately 60% of the sample was found to use substances, including 37% with current evidence of substance use disorders. Users (with and without substance use disorders), compared with nonusers, were significantly more likely to be male, be African-American, have lower educational attainment, have a recent period of homelessness, report more childhood conduct problems, have a history of major depression, have lower negative symptom and higher positive symptom scores on the Positive and Negative Syndrome Scale, and have a recent illness exacerbation. Individuals with comorbid substance use disorders were significantly more likely to be male, report more childhood conduct problems, have higher positive symptom scores on the Positive and Negative Syndrome Scale, and have a recent illness exacerbation. These analyses suggest that substance use disorders in schizophrenia are especially common among men with a history of childhood conduct disorder problems and that childhood conduct disorder problems are potent risk factors for substance use disorders in schizophrenia.

Correlates of Anger and Hostility in Iraq and Afghanistan War Veterans

OBJECTIVE As troops return from Iraq and Afghanistan to civilian life, clinicians are starting to grapple with how best to detect those at risk of postdeployment adjustment problems. Data reveal the presence of mental health problems in these soldiers, including posttraumatic stress disorder (PTSD), head injury, and alcohol abuse. Each of these conditions has been associated with elevated anger and hostility in veterans from previous conflicts. The authors sought to identify variables empirically related to anger and hostility in Iraq and Afghanistan veterans. METHOD A total of 676 veterans who served since September 11, 2001, and who volunteered to participate in research studies were interviewed with instruments designed to collect information on psychiatric symptoms, health, and possible postdeployment adjustment issues. The primary outcome measures were variables measuring aggressive impulses or urges, difficulty managing anger, and perceived problems controlling violent behavior. RESULTS The three outcome measures were each significantly associated with PTSD hyperarousal symptoms. Other PTSD symptoms were less strongly and less consistently linked to anger and hostility. Traumatic brain injury and alcohol misuse were related to the outcome variables in bivariate but not multivariate analyses. Distinct sets of demographic, historical, and military-related variables were associated with the different facets of anger and hostility measured. CONCLUSIONS The results underscore the need to tailor interventions individually to address anger and hostility effectively and to develop theoretically sophisticated, evidence-based knowledge to identify service members at risk of problematic postdeployment adjustment.

Persistent mild cognitive impairment in geriatric depression.

BACKGROUND Cognitive impairment often occurs with geriatric depression and impairments may persist despite remission of depression. Although clinical definitions of mild cognitive impairment (MCI) have typically excluded depression, a neuropsychological model of MCI in depression has utility for identifying individuals whose cognitive impairments may persist or progress to dementia. METHODS At baseline and 1-year follow-up, 67 geriatric patients with depression had a comprehensive clinical examination that included depression assessment and neuropsychological testing. We defined MCI by a neuropsychological algorithm and examined the odds of MCI classification at Year 1 for remitted depressed individuals with baseline MCI, and examined clinical, functional and genetic factors associated with MCI. RESULTS Fifty-four percent of the sample had MCI at baseline. Odds of MCI classification at Year 1 were four times greater among patients with baseline MCI than those without. Instrumental activities of daily living were associated with MCI at Year 1, while age and APOE genotype was not. CONCLUSIONS These results confirm previous observations that MCI is highly prevalent among older depressed adults and that cognitive impairment occurring during acute depression may persist after depression remits. Self-reported decline in functional activities may be a marker for persistent cognitive impairment, which suggests that assessments of both neuropsychological and functional status are important prognostic factors in the evaluation of geriatric depression.

Patient perceptions of coercion in mental hospital admission

In civil commitment the state applies its police and parens patriae powers in order to coerce mentally ill persons into treatment. Coercion, thus, is central to civil commitment. It also has been central in the mental health law debate over the justification of civil commitment of mentally ill patients. Civil libertarians, concerned with deprivations to free choice and movement, have argued for imposition of formal legal procedures and limitation of this coercion of mentally ill persons to those who are dangerous (La Fond & Durham, 1992; Morse, 1982; Wald & Friedman, 1978). Mental health practitioners, concerned with reducing symptoms and providing psychiatric care, have argued for minimal procedural and substantive limits on their ability to hospitalize and treat mentally disordered persons (Stone, 1975; Torrey, 1988; Treffert, 1981). Despite this debate, empirical researchers neglected development of the construct of coercion in psychiatric treatment (Hiday, 1992; Monahan et al., 1995); and only recently have they begun to lay the foundation conceptually and empirically to advance our understanding of it (Lidz & Hoge, 1993). In the substantial empirical literature on civil commitment, the existence of coercion was assumed to be inherent in the process while the focus was on other components of commitment such as characteristics of actors and rates of commitment. With few exceptions, researchers equated the legal category of involuntary patient with coercive practices.

Hippocampal Volume and Incident Dementia in Geriatric Depression

The authors investigated the role of baseline hippocampal volume on later clinical emergence of dementia in a group of older, non-demented depressed individuals. Subjects were 115 depressed, non-demented participants in a mental health clinical research center. All subjects were screened for dementia and agreed to have a magnetic resonance imaging (MRI) brain scan at baseline. Subjects were clinically evaluated by geriatric psychiatrists quarterly for up to 5 years and received annual neuropsychological testing. Bivariate analyses examined age, gender, race, educational level, baseline depression severity, age at depression onset, baseline Mini-Mental State Exam (MMSE), left and right hippocampal volume, and total cerebral volume. Age, baseline MMSE, total cerebral volume, and having a small left hippocampal volume were associated with later dementia and were included in subsequent survival analysis. Small left hippocampal volume was significantly associated with later dementia (hazard ratio=2.762). Small left hippocampal size on neuroimaging may be a marker for dementia in depressed patients who have not yet met criteria for a clinical diagnosis of a dementing disorder.