Showing papers in "Journal of Neuropsychiatry and Clinical Neurosciences in 2010"

The Human Amygdala

Abstract: Building on pioneering animal studies, and making use of new, noninvasive techniques for studying the human brain, research on the human amygdala has blossomed in recent years. This comprehensive volume brings together leading authorities to synthesize current knowledge on the amygdala and its role in psychological function and dysfunc tion. Initial chapters discuss how animal models have paved the way for work with human subjects. Next, the book examines the amygdalas involvement in emotional processing, learning, memory, and social interaction. The final section presents key advances in understanding specific clinical disorders: anxiety disorders, depression, schizophrenia, autism, and Alzheimers disease. Illustrations include 39 color plates.

“Frontal” Behaviors Before the Diagnosis of Huntington’s Disease and Their Relationship to Markers of Disease Progression: Evidence of Early Lack of Awareness

Abstract: Huntington's disease has been linked with fronto-subcortical neuropathology and behaviors consistent with this dysfunction. Little is known about these "frontal" behaviors in the earliest phase of the illness. Comparisons between participants in the Predict-HD study (745 "expansion-positive" and 163 "expansion-negative" control subjects) on the Frontal System Behavior Scale looked for evidence of frontal behaviors, including apathy, disinhibition, and executive dysfunction. The authors were also able to compare participant and companion reporting of these frontal behaviors as a possible indication of awareness of behaviors. Expansion-positive individuals reported significantly more of these frontal behaviors than expansion-negative peers. Self- and companion-reported frontal behaviors were related to other Huntington's disease markers. Expansion-positive participants closest to Huntington's disease diagnosis showed greater discrepancies with companions on ratings of frontal behaviors. Even though most are more than 10 years from Huntington's disease diagnosis, mild frontal behaviors were present in this prediagnosed sample, which might make these behaviors useful as markers for Huntington's disease onset. Participant/companion discrepancies, especially closest to Huntington's disease diagnosis, might suggest early lack of awareness in these individuals.

Neuropsychological Outcomes of Older Breast Cancer Survivors: Cognitive Features Ten or More Years After Chemotherapy

Abstract: The authors examined the long-term cognitive implications of cancer treatment among breast cancer survivors over 65 years old who received treatment during midlife. Thirty women survivors were matched with 30 noncancer, healthy older adults in terms of age, education, and IQ. The cancer survivors scored significantly lower in the cognitive domains of executive functioning, working memory, and divided attention, reflecting potential dysfunction in frontal-subcortical brain regions. Our findings suggest that among breast cancer survivors who remain disease-free for more than a decade, the previous cancer treatment may further augment cognitive dysfunction associated with age-related brain changes.

Psychopharmacological Neuroprotection in Neurodegenerative Disease: Assessing the Preclinical Data

Abstract: This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

Predictors of new-onset depression after mild traumatic brain injury.

Abstract: Mild traumatic brain injury (TBI) is the most common form of TBI. Most people recover after mild TBI, but a small percentage continues to have persistent problems, predominantly depression. There is, however, minimal literature on the risk factors associated with mild TBI depression. In a sample of 43 mild TBI patients, followed longitudinally for 1 year, the prevalence of new-onset depression was found to be 18%. Older age and presence of frontal subdural hemorrhage were the only two significant findings noted in the depressed group compared with the nondepressed group. Identifying risk factors for mild TBI depression can aid in early diagnosis and treatment.

A hypothesized role for dendritic remodeling in the etiology of mood and anxiety disorders.

Abstract: An elegant theory that links hippocampal neurogenesis to mood and anxiety disorders and to the mechanism of action of antidepressant drugs has gained widespread attention. However, depression and anxiety disorders involve multiple areas of the brain, such as the amygdala and prefrontal cortex, where neurogenesis does not appear to occur in the adult mammalian brain. A complementary theory is proposed here in which neurogenesis is seen as an epiphenomenon of a more widespread alteration in dendritic length and spine number. According to this theory, exposure to chronic stress and stressful life events increases excitotoxic glutamatergic neurotransmission in multiple brain areas. To protect neurons from consequent apoptosis, dendrites retract and spine number decreases, thus limiting the number of exposed glutamate receptors. Drugs that reduce glutamatergic neurotransmission under these circumstances, many of which have already been shown helpful in treating mood and anxiety disorders, may prevent this dendritic retraction and thus protect synaptic connections throughout the brain.

Subgenual Cingulate Theta Activity Predicts Treatment Response of Repetitive Transcranial Magnetic Stimulation in Participants With Vascular Depression

Abstract: 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.

Anosognosia is a significant predictor of apathy in Alzheimer's disease.

Abstract: Anosognosia and apathy are among the most common behavioral and psychological disorders of Alzheimer's disease and are significantly associated in cross-sectional studies. The aim for this study was to carry out for the first time a longitudinal assessment of this association with the aim of clarifying the predictive role between anosognosia and apathy in Alzheimer's disease. A consecutive series of 213 patients with probable Alzheimer's disease were assessed for the presence of apathy and anosognosia using a specific neuropsychiatry assessment. One hundred fifty four of the patients (72%) had a follow-up assessment between 1 and 4 years after the baseline evaluation. Patients with anosognosia at baseline had a significant increase in apathy scores during follow-up relative to patients without anosognosia at both assessments. Conversely, patients with or without apathy had an increase of similar magnitude in anosognosia scores. In conclusion, anosognosia is a significant predictor of apathy in Alzheimer's disease. This may be related to a specific pattern of progression of neuropathology and/or to poor adjustment of Alzheimer's disease patients with poor insight into their functional deficits.

Cotard syndrome in neurological and psychiatric patients.

Abstract: The authors describe the frequency and characteristics of Cotard syndrome among neurological and psychiatric inpatients at a tertiary referral center. All inpatients from the National Institute of Neurology of Mexico (March 2007-May 2009) requiring neuropsychiatric consultation were reviewed. Among 1,321 inpatient consultations, 63.7% had neurological disease and one (0.11%) had viral encephalitis and Cotard syndrome. Of inpatients, 36.2% had pure psychiatric disorders and three (0.62%) had Cotard syndrome, associated with psychotic depression, depersonalization, and penile retraction (koro syndrome). This review discusses potential mechanisms for Cotard syndrome, including the role of a perceptual-emotional dissociation in self-misattribution in the delire des negations.

Pediatric stroke: plasticity, vulnerability, and age of lesion onset.

Abstract: The authors aim to investigate brain plasticity and vulnerability through the study of the relationship of age at the time of brain injury and neurocognitive and psychiatric outcome. Children with early stroke performed more poorly compared with children with late stroke in a wide variety of domains including intellectual function, language, memory, visuospatial function, academic function, and psychiatric problems. The exception to this pattern was that children with late stroke performed more poorly in two of three executive function tests. These findings suggest that in children with focal brain injury, as in those with more diffuse brain insults, younger age at injury predicts worse neurocognitive outcomes, although this may not apply to selected executive function outcomes. Adverse psychiatric outcome after early stroke is less direct but is evident in terms of severity in affected cases.

Consequences of Aggressive Behavior in Patients With Dementia

Abstract: This study examined aggression as a predictor of nursing-home placement, injuries, use of restraints, and use of health services in community-dwelling patients with newly diagnosed dementia. Participants were identified from 2001-2004 Veterans Administration databases; all had a new diagnosis of dementia and no aggression. Patients and caregivers were evaluated for aggression, using the Cohen-Mansfield Agitation Inventory-aggression subscale, and other outcomes for 2 years, with outcome rates compared between patients who did or did not develop aggression and between pre- and postaggressive periods. Of 215 patients, 88 became aggressive, associated with significantly increased use of psychotropic medication (p< or =0.04), injuries (p< or =0.0001), and nursing-home placement (p< or =0.004).

Neuropsychological consequence of soccer play in adolescent U.K. School team soccer players.

Abstract: To assess mild head injury effects in adolescent soccer players, neuropsychological performance across school team soccer players, rugby players and noncontact sport players was assessed in a quasi-experimental cross-sectional design. One hundred eighty-five males were tested (ages 13-16; response rate 55%) and 86 contributed data to the analyses after exclusion for recent concussion and overlapping sports participation. Soccer players showed lower premorbid intellectual functioning, but neither soccer players nor rugby players showed neuropsychological decrement compared with noncontact sport players. Cumulative heading did not predict neuropsychological performance. While no specific attribute of soccer was linked with neuropsychological impairment, head injury predicted reduced attention for all participants.

Hippocampal volumes in adults with bipolar disorder.

Abstract: Functional neuroimaging studies have implicated the hippocampus formation in the pathophysiology of bipolar disorder, but findings from volumetric studies have been less consistent. The authors aim to further investigate the existence of volumetric abnormalities in the hippocampus of individuals with bipolar disorder. In addition to methodological inconsistencies, many previous studies have been lacking clinical robustness with respect to characterizing bipolar patients and comparison subjects. Hence, the present study matched the groups closely across a number of demographic parameters. Using MRI, hippocampal volumes of 24 bipolar patients were compared to 24 sex-, age-, and education-matched comparison subjects, and these findings were further investigated in relation to both illness and treatment factors. A significantly larger (8.5%) right hippocampus was seen in bipolar patients than in comparison subjects, and this difference was not associated with a history of psychosis, familial illness, or lithium treatment, after controlling for potential confounds. Patients reporting fewer affective episodes did however have significantly larger left hippocampus volumes than comparison subjects. The authors found that the left hippocampus was larger in a group of adult bipolar subjects relative to the healthy comparison group. The reason for this is unclear, but in this sample, it was not associated with family history, psychotic features, or medication exposure. A negative association was found between left hippocampal volume and number of episodes or duration of illness, suggesting the hippocampus might be larger in the early phase of bipolar disorder but becomes smaller with time.

EEG Findings in Burnout Patients

Abstract: The concept of burnout remains enigmatic since it is only determined by behavioral characteristics. Moreover, the differential diagnosis with depression and chronic fatigue syndrome is difficult. EEG-related variables in 13 patients diagnosed with burnout syndrome were compared with 13 healthy comparison subjects in order to explore the existence of neurobiological markers for burnout. Burnout patients showed reduced P300 amplitude, a lower alpha peak frequency and reduced beta power. These EEG-related differences in burnout patients differ from those described in the literature in depression and chronic fatigue patients. Our preliminary findings suggest that burnout might be considered as a separate clinical syndrome.

Correlates of Apathy in Huntington’s Disease

Abstract: The authors aim to study prevalence and clinical correlates of apathy in Huntington's disease. Apathy was defined as an Apathy Scale score >= 14 points in 152 Huntington's disease mutation carriers and 56 noncarriers. Correlates of apathy were analyzed cross-sectionally in mutation carriers using multivariable logistic regression analysis. Forty-nine (32%) Huntington's disease mutation carriers showed apathy compared to none of the noncarriers. After exclusion of 10 depressed patients, apathy was independently associated with male sex, worse global functioning, and higher use of neuroleptics and benzodiazepines. (The Journal of Neuropsychiatry and Clinical Neurosciences 2010; 22:287-294)

Clock Drawing Test Ratings by Dementia Specialists: Interrater Reliability and Diagnostic Accuracy

Abstract: The authors conducted a study of clock drawing test scoring by dementia specialists to determine interrater reliability and diagnostic accuracy. The authors randomly assigned 25 clocks from each of six predetermined groups based on consensus diagnosis (cognitive comparison subjects, subjects with a memory complaint but with normal neuropsychological testing, subjects with probable and possible mild cognitive impairment, and subjects with possible and probable Alzheimer's disease) to dementia specialists for blinded scoring using a binary yes/no impairment system and a 0-10 scale as subjectively determined by each individual clinician rater. The authors collapsed the six groups into three (comparison subjects, mild cognitive impairment patients, and Alzheimer's disease patients) and analyzed interrater reliability, sensitivity, and specificity for consensus diagnosis of mild cognitive impairment and Alzheimer's disease. The authors found excellent interrater reliability, sensitivity, and specificity for predicting consensus diagnosis. The 0-10 clock drawing test rating scale was more predictive of consensus diagnosis than the binary impairment scale. Based on rating systems, clock drawing test scoring by dementia clinicians had excellent interrater reliability and sensitivity for differentiating the mild Alzheimer's disease subjects from comparison subjects.

The Use of a Series of Ketamine Infusions in Two Patients With Treatment-Resistant Depression

Abstract: Treatment-resistant depression often leads to increased morbidity and disability. The authors report the use of ketamine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist, in two patients with treatment-resistant depression. Multiple ketamine treatments may provide an effective rapid antidepressant effect with prolonged benefit.

Asymmetrical contribution of brain structures to treatment-resistant depression as illustrated by effects of right subgenual cingulum stimulation.

Abstract: Major depressive disorder is one of the most common psychiatric disorders, with a worldwide lifetime prevalence rate of 10%-20% in women and a slightly lower rate in men. While many patients are successfully treated using established therapeutic strategies, a significant percentage of patients fail to respond. This report describes the successful recovery of a previously treatment-resistant patient following right unilateral deep brain stimulation of Brodmann's area 25. Current therapeutic approaches to treatment-resistant patients are reviewed in the context of this case with an emphasis on the role of the right and left hemispheres in mediating disease pathogenesis and clinical recovery.

White Matter Correlates of Apathy in HIV-Positive Subjects: A Diffusion Tensor Imaging Study

Abstract: Apathy is commonly reported by patients infected with HIV. No previous work has assessed the relationship between white matter and apathy in HIV. The authors aimed to determine whether apathy in HIV reflects a direct effect of the virus on subcortical brain regions or a secondary neuropsychiatric symptom. Thirteen HIV+ participants with apathy, 13 HIV+ participants with no apathy, and 10 healthy comparison subjects were examined using diffusion tensor imaging in the region of the anterior cingulate and corpus callosum. Results of the study confirmed the hypothesis which anticipated changes associated with apathy in white matter tracts that relay through the medial prefrontal cortex.

Neuroanatomical Correlates of Depression in Post Traumatic Brain Injury: Preliminary Results of a Pilot Study

Abstract: The authors present preliminary results from a pilot study on patterns of brain injury associated with incident major depression after traumatic brain injury (TBI). Brain metabolite ratios, regional brain volumes, and cognitive performance were compared between 10 subjects with incident major depression post-TBI and seven TBI patients without major depression. TBI-depressed participants performed poorly on tests of frontotemporal functioning, had lower choline/creatine and N-acetylaspartate/creatine ratios in the right basal ganglia and had lower regional brain volumes in the right frontal, left occipital, and temporal lobes. The results suggest a possible role of frontotemporal lobe and basal ganglia pathology in depression after TBI.

Relationship between cognitive status at admission and incident delirium in older medical inpatients.

Abstract: To evaluate the relationship between cognitive status and incident delirium, 291 geriatric patients on internal medicine wards were evaluated on admission with the Mini-Mental State Examination (MMSE) and Confusion Assessment Method-Spanish. Those with incident delirium were assessed using the Delirium Rating Scale-Revised-98 (DRS-R98). Delirium incidence was 11.7%, and 82 patients (28.2%) had cognitive deficits on MMSE. As cognitive impairment worsened, the risk for delirium increased linearly, and for each unit of MMSE worsening the DRS-R98 severity score worsened 0.4 points (F=5.39, df=1, p=0.027). Optimal MMSE cutoff score from receiver-operating characteristic curve analysis was 24.5. Even mild cognitive deficits increase delirium risk and severity.

The Role of Mild Depression in Sleep Disturbance and Quality of Life in Parkinson’s Disease

Abstract: This study examined depressive symptoms, sleep disturbance, and quality of life in 35 patients with Parkinson’s disease. Results showed that nocturnal sleep disturbance, depressive symptoms, and motor disease severity accounted for over two-thirds of the variance in quality of life scores. Depression was the largest predictor of quality of life, uniquely explaining 21% of the variance. Nocturnal sleep disturbance was associated with depressive symptoms as well as with daytime sleepiness. Overall, these data highlight the need to screen patients for even mild levels of depression because its relationship with sleep and quality of life are evident early in the disease course.

Altered Attribution of Intention in Tourette's Syndrome.

Abstract: Core symptoms of Tourette's syndrome are assumed to result from inhibitory dysfunction, which could also impair theory of mind. Here the authors report evidence for theory of mind difficulties: patients exhibit deficits in recognizing faux pas and understanding intentionality. (The Journal of Neuropsychiatry and Clinical Neurosciences 2010; 22:348-351)

Increased Cortisol Levels and Anticholinergic Activity in Cognitively Unimpaired Patients

Abstract: Increased patients' serum anticholinergic activity (SAA) is described as a marker of cognitive dysfunction and can be influenced by different exogenous and endogenous factors. The role of cortisol in relation to SAA and cognition in perioperative conditions has not been investigated so far. In 30 men scheduled for urological surgery, the authors determined SAA and cortisol levels in blood and CSF and conducted neuropsychological testing in two subgroups with comparable pre- and intraoperative characteristics, one group with low SAA (mean=2.4 [SD=0.9], n=23) and the other with high SAA (mean=5.1 [SD=2.4], n=7) values. Increased SAA was associated with two times the number of anticholinergic medications but not with patients' age, medical history or impaired cognition. A significant linear correlation was detected between anticholinergic activities and cortisol levels. Thus, endogenous factors such as patients' stress levels should be taken into account for interpretation of the role of SAA.

The brainstem: anatomy, assessment, and clinical syndromes.

Abstract: Cover and Figure 1. The internal anatomy of the brainstem is presented in a simplified, color-coded format. Cover. The approximate locations and extents of nuclei that are important sources for a particular neurotransmitter are colorcoded onto a sagittal magnetic resonance image. Figure 1. The approximate locations and extent of major tracts and nuclei are colorcoded onto simplified axial illustrations of brainstem sections (left panel). The most common pattern of arterial territories is also presented (right panel). All illustrations are oriented in the radiographic perspective.

Nonclinical Obsessive-Compulsive Symptoms and Executive Functions in Schizophrenia

Abstract: The impact of nonclinical obsessive-compulsive symptoms (OCS) on neuropsychological functioning in schizophrenia has received little investigation. The authors evaluated whether severity and subtype of OCS are associated with executive functioning in schizophrenia. Twenty-nine patients with schizophrenia and 32 healthy comparison subjects completed questionnaire and performance-based measures of executive functioning. Overall OCS severity in patients was associated with poorer monitoring and cognitive flexibility. 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 nonclinical OCS subtypes contributes to the heterogeneity of executive functions in schizophrenia.

The Use of DSM-IV and ICD-10 Criteria and Diagnostic Scales for Delirium Among Cardiac Surgery Patients: Results From the IPDACS Study

Abstract: Diagnostic accuracy of different diagnostic systems in estimating the incidence of delirium among surgery patients has not been investigated to date. Therefore, the authors evaluated the frequency of delirium according to DSM-IV and ICD-10 criteria and the cutoff values of the Memorial Delirium Assessment Scale (MDAS) and Delirium Index in 563 patients undergoing cardiac surgery. DSM-IV criteria were found as more inclusive, while ICD-10 criteria were more restrictive in establishing a diagnosis of postoperative delirium. The cutoff scores of 10 on the MDAS and 7 on the Delirium Index were optimal to the presence or absence of delirium.

Impaired Awareness of Deficits and Neuropsychiatric Symptoms in Early Alzheimer’s Disease: The Danish Alzheimer Intervention Study (DAISY)

Abstract: Impaired awareness may be associated with increased neuropsychiatric symptoms in moderate to severe Alzheimer's disease, but relatively little is known about the association in early Alzheimer's disease. The aim of this study was to investigate if impaired awareness was associated with a higher frequency of neuropsychiatric symptoms in early Alzheimer's disease. In a Danish multicenter study, 321 patients with MMSE score > or =20 were evaluated. Patients with poor insight had significantly more neuropsychiatric symptoms than patients with full insight. When patients had increasing neuropsychiatric symptoms, caregivers reported higher levels of distress.