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1.  Who Qualifies for Deep Brain Stimulation for OCD? Data from a Naturalistic Clinical Sample 
A few patients with obsessive-compulsive disorder (OCD) remain severely impaired despite exhausting best-practice treatments. For them, neurosurgery (stereotactic ablation or deep brain stimulation) might be considered. We investigated the proportion of treatment-seeking OCD patients, in a naturalistic clinical sample, who met contemporary neurosurgery selection criteria. Using comprehensive baseline data on diagnosis, severity, and treatment history for adult patients from the NIMH-supported Brown Longitudinal OCD Study, only two of 325 patients met screening criteria for neurosurgery. This finding prompts consideration of new models for clinical trials with limited samples as well as methods of refining entry criteria for such invasive treatments.
PMCID: PMC4093791  PMID: 24515679
Obsessive-compulsive disorder; Deep brain stimulation; Neurosurgery; Humanitarian device exemption
2.  Neuropsychological Outcomes Following Psychosocial Intervention for Depression in Parkinson’s disease 
The purpose of this paper is to describe neuropsychological outcomes in people with Parkinson’s disease (PD) following their participation in an NIH-sponsored, randomized-controlled trial of cognitive-behavioral treatment for depression. Improvements in mood were associated with modest gains in verbal memory and executive functioning, over the 10-week treatment period, and accounted for greater variance in neuropsychological outcomes at the end-of-treatment, than other known correlates of cognitive functioning in PD, such as disease severity, age, and education. Baseline working memory and executive skills were also associated with depression improvement over time.
PMCID: PMC4144827  PMID: 24275895
Parkinson’s disease; depression; cognition; psychosocial intervention
3.  Preliminary Evidence for Sensitive Periods in the Effect of Childhood Sexual Abuse on Regional Brain Development 
Volumetric MRI scans from 26 women with repeated episodes of childhood sexual abuse (CSA), and 17 healthy women (18–22 years) were analyzed for sensitive periods effects on hippocampal and amydgala volume, frontal cortex gray matter volume and corpus callosum area. Hipppocampal volume was reduced in association with CSA at 3–5 years (β=−0.69, p<0.0001) and 11–13 years (β=−0.25, p<0.05). Corpus callosum was reduced with CSA at 9–10 years (β=−0.44, p<0.005), and frontal cortex was attenuated in subjects with CSA at ages 14–16 (β=−0.48, p<0.005). Brain regions have unique windows of vulnerability to the effects of traumatic stress.
PMCID: PMC4270804  PMID: 18806232
hippocampus; frontal cortex; corpus callosum childhood sexual abuse; stress; maltreatment; adolescents
4.  Associations of Sleep Disturbance Symptoms with Health-Related Quality of Life in Parkinson’s Disease 
We examined associations of different sleep disturbance symptoms with health-related quality of life (HRQOL) in 153 adults with Parkinson’s disease (PD). PD patients reported more snoring, sleep inadequacy, daytime somnolence, and sleep maintenance problems than the general population (p<0.001). Symptoms having the broadest and strongest unique associations with generic HRQOL (8 scales; 2 composites of SF-36) were daytime somnolence (5 scales; 1 composite), sleep initiation (8 scales; 2 composites), and awakening short of breath or with headache (6 scales; 2 composites) (p’s<0.05). Associations of selected sleep disturbance symptoms – some unanticipated – suggest that assessing specific symptoms is worthwhile in clinical care.
PMCID: PMC3960993  PMID: 24247858
sleep disturbance; Parkinson’s disease; health-related quality of life
5.  Disorganized Symptoms and Executive Functioning Predict Impaired Social Functioning in Subjects at Risk for Psychosis 
Predictors of social functioning deficits were assessed in 22 individuals “at risk” for psychosis. Disorganized symptoms and executive functioning predicted social functioning at follow-up. Early intervention efforts that focus on social and cognitive skills are indicated in this vulnerable population.
PMCID: PMC4113423  PMID: 22231319
Prodromal; At-Risk; Schizophrenia; Clinical; Social Functioning; Neurocognition
8.  Non-Clinical Obsessive Compulsive Symptoms and Executive Functions in Schizophrenia 
The impact of non-clinical obsessive compulsive symptoms (OCS) on neuropsychological functioning in schizophrenia has received little investigation. We evaluated whether severity and subtype of OCS are associated with executive functioning in schizophrenia. Twenty-nine patients with schizophrenia and 32 healthy subjects completed questionnaire and performance-based measures of executive functioning Overall OCS severity in patients was associated with poorer monitoring and cognitive flexibility per a questionnaire. Obsessing, hoarding, and checking were related to poorer executive functioning in daily life. Performance-based scores showed few correlations with OCS. Findings indicate that severity of non-clinical OCS subtypes contribute to the heterogeneity of executive functions in schizophrenia.
PMCID: PMC4075772  PMID: 20686137
Schizophrenia; OCD; Executive Function; Neuropsychology
9.  Dopaminergic Challenge With Bromocriptine One Month After Mild Traumatic Brain Injury: Altered Working Memory and BOLD Response 
Catecholamines, particularly dopamine, modulate working memory (WM). Altered sensitivity to dopamine might play a role in WM changes observed after traumatic brain injury (TBI). Thirty-one healthy controls (HC) and 26 individuals with mild TBI (MTBI) 1 month after injury were challenged with bromocriptine versus placebo before administration of a verbal WM functional MRI task. Bromocriptine was associated with improved WM performance in the HC but not the MTBI group. On bromocriptine, the MTBI group showed increased activation outside of a task-specific region of interest. Findings are consistent with the hypothesis that individuals with MTBI have altered responsivity to dopamine.
PMCID: PMC4074527  PMID: 21948888
10.  Apathy is associated with increased amyloid burden in mild cognitive impairment 
Apathy is the most common neuropsychiatric symptom in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. We sought to determine whether apathy is associated with cortical amyloid burden measured by Pittsburgh Compound B (PiB) positron emission tomography (PET) and regional hypometabolism measured by 18F-fluorodeoxyglocuse (FDG) PET in MCI. We found a significant association between increased apathy (lower Apathy Evaluation Scale score) and greater cortical PiB retention independent of age (prs=−0.46, p=0.03), but no significant association between apathy and regional FDG metabolism. These results suggest that increased apathy is associated with greater amyloid burden but not regional hypometabolism in MCI.
PMCID: PMC3957217  PMID: 24247857
Alzheimer’s disease; amyloid; apathy; 18F-flourodeoxyglucose; mild cognitive impairment; Pittsburgh Compound B; positron emission tomography
11.  Are Selective Serotonin Reuptake Inhibitors Associated With Greater Apathy in Parkinson’s Disease? 
Apathy is a common neuropsychiatric feature of Parkinson’s disease (PD), but little is known of relationships between apathy and specific medications in PD. Following a retrospective database and chart review of 181 Parkinson’s patients, relationships between Apathy Scale scores and use of psychotropic and antiparkinsonian medications were examined with multiple regression. Controlling for age, sex, education, and depression, the use of selective serotonin reuptake inhibitors (SSRIs), but not other antidepressants, was associated with greater apathy. Use of monoamine oxidase B inhibitors was associated with less apathy. Longitudinal studies are needed to evaluate a potential SSRI-induced apathy syndrome in PD.
PMCID: PMC3759813  PMID: 23037646
12.  Elevated Neurobehavioral Symptoms are Associated with Everyday Functioning Problems in Chronic Methamphetamine Users 
Chronic methamphetamine (MA) use is commonly associated with neural injury and neurocognitive deficits. We examined the nature and correlates of self-reported neurobehavioral symptoms (i.e., apathy, disinihibition, and executive dysfunction) in 73 individuals with histories of MA dependence (MA+) and 85 comparison participants with comparable demographics and risk histories. MA+ individuals endorsed significantly more severe neurobehavioral symptoms on the Frontal Systems Behavioral Scale (FrSBe), especially disinhibition and executive dysfunction. Elevations in neurobehavioral symptoms were independent of common comorbidities, including hepatitis C infection, Attention-Deficit/Hyperactivity Disorder, mood disorders, and other substance use factors. Notably, the severity of neurobehavioral symptoms were uniquely associated with self-reported decrements in instrumental activities of daily living in the MA dependent sample. Findings indicate that chronic MA users may experience elevated neurobehavioral symptoms of disinhibition and executive dysfunction, potentially increasing their risk of functional declines.
PMCID: PMC3735421  PMID: 23037647
Methamphetamine; Substance abuse; Executive dysfunction; Behavioral disinhibition; Neuropsychological assessment; Activities of daily living
13.  Subgenual Cingulate Theta Activity Predicts Treatment Response of Repetitive Transcranial Magnetic Stimulation in Participants With Vascular Depression 
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. Increased metabolism in the anterior cingulate cortex (ACC) is a known predictor for antidepressant response. The authors assessed whether increased theta power within the ACC predicts rTMS response in participants with vascular depression. Sixty-five participants were randomized to active or sham rTMS. Outcome was assessed using the Hamilton Depression Rating Scale. Electroencephalography was obtained, and comparisons were made among each group with a normative database using low-resolution electromagnetic tomography. Results suggest that vascular depression participants respond well to rTMS and that increased low-theta power in the subgenual ACC predicts response to rTMS.
PMCID: PMC3688059  PMID: 20160213
14.  [No title available] 
PMCID: PMC3647459  PMID: 21037120
15.  [No title available] 
PMCID: PMC3641646  PMID: 21304142
16.  [No title available] 
PMCID: PMC3640485  PMID: 23487198
17.  [No title available] 
PMCID: PMC3641161  PMID: 20160209
18.  Differential Effects of Executive Functioning on Suicide Attempts 
Suicide is common among individuals with psychiatric illness; executive functioning may be associated with suicide risk. The authors examined demographic, clinical, and executive-functioning variables in suicide ideators and suicide attempters, hypothesizing that attempters would demonstrate poorer executive-functioning skills. Seventy-seven participants with psychiatric illness completed a neuropsychological battery while hospitalized or residing in crisis-houses after expressing suicidal ideation (N=40) or making a suicide attempt (N=37). Logistic regression predicted suicide Ideator versus suicide Attempter status; suicide Attempters exhibited poorer inhibition but better problem-solving ability than suicide Ideators. Suicide attempt risk may be associated with better problem-solving skills, but worse inhibitory control.
PMCID: PMC3626287  PMID: 21677246
19.  Semantic Cueing Improves Category Verbal Fluency in Persons Living with HIV Infection 
HIV-associated neurocognitive disorders (HAND) remain highly prevalent in the era of cART, but there are no validated psychological interventions aimed at improving cognitive outcomes. This study sought to determine the potential benefit of semantic cueing on category fluency deficits, which are prevalent in HIV and impact daily functioning. Eighty-six HIV-infected individuals and 87 demographically matched seronegative participants were administered a standard (i.e., uncued) and a cued category fluency task. Results revealed significant improvements in cued versus uncued performance in HIV, particularly for persons with lower levels of education. The cueing benefit observed may inform rehabilitation efforts aimed at ameliorating HAND.
PMCID: PMC3396423  PMID: 22772666
infectious disease; verbal fluency; semantic memory; cognitive rehabilitation; executive functions; cognitive neuropsychology
20.  The Role of HIV Infection, Cognition, and Depression in Risky Decision-Making 
The authors examined the impact of HIV, cognitive dysfunction, and depression on decision-making. HIV+ (N=100) and HIV− (N=26) participants were administered a comprehensive neuropsychological battery, a modified version of the Iowa Gambling Task, and a measure of depressive symptoms. HIV+ participants demonstrated more difficulties in learning the gambling task than did HIV− participants. Executive functioning and depression emerged as strong predictors of gambling task performance. Depression partially mediated the relationship between executive functioning and gambling performance. Our findings suggest that HIV infection, executive dysfunction, and depression place individuals at risk for poor decision-making.
PMCID: PMC3608191  PMID: 23037648
21.  Antiretroviral Adherence and the Nature of HIV-Associated Verbal Memory Impairment 
The authors investigated the relationship between antiretroviral adherence and HIV-associated verbal memory impairment. HIV-positive participants demonstrated poorer verbal memory than HIV-negative participants. Both good (≥90%) and poor (<90%) adherers displayed encoding deficits as compared with controls, but only poor adherers exhibited retrieval deficits. Encoding deficits primarily accounted for reduced delayed recall in good adherers, but both encoding and retrieval deficits accounted for reduced delayed recall in poor adherers. The retrieval difference between the adherence groups might be explained by a neuroprotective effect of good antiretroviral adherence or preexisting HIV-related retrieval deficits that result in poorer adherence.
PMCID: PMC3603356  PMID: 21948894
22.  Sustained Attention Deficits Among HIV-Positive Individuals With Comorbid Bipolar Disorder 
Difficulties with sustained attention have been found among both persons with HIV infection (HIV+) and bipolar disorder (BD). The authors examined sustained attention among 39 HIV+ individuals with BD (HIV+/BD+) and 33 HIV-infected individuals without BD (HIV+/BD−), using the Conners’ Continuous Performance Test–II (CPT–II). A Global Assessment of Functioning (GAF) score was also assigned to each participant as an overall indicator of daily functioning abilities. HIV+/BD+ participants had significantly worse performance on CPT–II omission errors, hit reaction time SE (Hit RT SE), variability of SE, and perseverations than HIV+/BD− participants. When examining CPT–II performance over the six study blocks, both HIV+/BD+ and HIV+/BD− participants evidenced worse performance on scores of commission errors and reaction times as the test progressed. The authors also examined the effect of current mood state (i.e., manic, depressive, euthymic) on CPT–II performance, but no significant differences were observed across the various mood states. HIV+/BD+ participants had significantly worse GAF scores than HIV+/BD− participants, which indicates poorer overall functioning in the dually-affected group; among HIV+/BD+ persons, significant negative correlations were found between GAF scores and CPT–II omission and commission errors, detectability, and perseverations, indicating a possible relationship between decrements in sustained attention and worse daily-functioning outcomes.
PMCID: PMC3575087  PMID: 22450615
23.  Underlying Neurobiology and Clinical Correlates of Mania Status-Post Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s disease: A Review of the Literature 
Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson’s disease (PD).
We review the current literature to identify the clinical correlates associated with STN DBS-induced hypomania/mania in PD patients.
Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male patients and/or early onset PD.
STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanism(s) of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight towards development of future DBS mood stabilization therapies.
PMCID: PMC3570815  PMID: 22450620
Parkinson’s disease; mania; subthalamic nucleus (STN); deep brain stimulation (DBS)
24.  Familial Aggregation of Panic Disturbances in Parkinson’s Disease 
Panic disorder has an elevated prevalence in Parkinson’s disease (PD). To explore the basis for this co-occurrence, the familial aggregation of panic disorder was examined in patients with PD. Probands and relatives of patients with PD and panic disorder (PD-PANIC; N=20, N=115) and control probands with PD and no active psychiatric illness (PD-NA; N=17, N=108) were interviewed by phone, using a structured interview to determine panic status. Lifetime prevalence of panic and “panic-like” disorders was higher in PD-PANIC than in PD-NA relatives. Panic and “panic-like” disorders are familial disorders in PD.
PMCID: PMC3547673  PMID: 22231313
25.  Diffusion Tensor Imaging of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Alzheimer’s Dementia 
Neuropsychiatric symptoms (NPS) occur frequently in mild cognitive impairment (MCI) and Alzheimer’s dementia (AD). We examined the relationship between NPS and white matter integrity in these conditions. Twenty two individuals with MCI and 23 with mild AD underwent clinical assessments including the Neuropsychiatric Inventory Questionnaire and 3.0 Tesla magnetic resonance scans. Fractional anisotropy (FA) was measured in the following manually-drawn regions of interest (ROI): fornix, cingulum bundle, splenium, and cerebral peduncles (control region). The probability of having NPS by tertile of ROI FA was assessed using logistic regression. Because associations were similar within MCI and AD groups, the two groups were combined. Compared to those in the highest tertile, participants within the lowest anterior cingulum (AC) FA tertile were more likely to exhibit irritability, agitation, dysphoria, apathy, and nighttime behavioral disturbances (p<0.05). After adjusting for MMSE, participants in the lowest vs. highest tertile of AC FA were more likely to report irritability (OR: 7.21, p=0.041). Using DTI, low AC FA was associated with increased odds of irritability in mild AD and MCI participants. Further imaging studies are necessary to elucidate the role of the AC in the pathophysiology of NPS in AD and MCI.
PMCID: PMC3533244  PMID: 23224456
Diffusion tensor imaging; Alzheimer’s disease; Mild cognitive impairment; Neuropsychiatric symptoms

Results 1-25 (69)