Brett Y. Lu

Effect of Catechol O-Methyltransferase Val158Met Polymorphism on the P50 Gating Endophenotype in Schizophrenia

BACKGROUND Studies have implicated prefrontal dopamine in cortical information filtering. Deficit in stimulus filtering, an endophenotype of schizophrenia, can be demonstrated using the auditory P50 paired-click gating paradigm. The role of prefrontal dopamine on P50 gating was investigated, using catechol-O-methyltransferase (COMT) valine (val)(158)methionine (met) polymorphism as a predictor of prefrontal dopamine activity. METHODS Twenty-five comparison and 42 schizophrenia subjects underwent P50 gating measurement and COMT genotyping. RESULTS In the combined sample, COMT polymorphism accounted for a unique 10% of gating variance (p = .02), after variance due to diagnosis, smoking status, and antipsychotic use was removed. Valine homozygous individuals exhibited the greatest gating deficit. CONCLUSIONS Valine homozygous individuals are more likely to have gating deficits, supporting COMT as a genetic determinant of the P50 endophenotype, as well as a role for prefrontal dopamine in auditory filtering.

Frontal and superior temporal auditory processing abnormalities in schizophrenia

Background Although magnetoencephalography (MEG) studies show superior temporal gyrus (STG) auditory processing abnormalities in schizophrenia at 50 and 100 ms, EEG and corticography studies suggest involvement of additional brain areas (e.g., frontal areas) during this interval. Study goals were to identify 30 to 130 ms auditory encoding processes in schizophrenia (SZ) and healthy controls (HC) and group differences throughout the cortex. Methods The standard paired-click task was administered to 19 SZ and 21 HC subjects during MEG recording. Vector-based Spatial–temporal Analysis using L1-minimum-norm (VESTAL) provided 4D maps of activity from 30 to 130 ms. Within-group t-tests compared post-stimulus 50 ms and 100 ms activity to baseline. Between-group t-tests examined 50 and 100 ms group differences. Results Bilateral 50 and 100 ms STG activity was observed in both groups. HC had stronger bilateral 50 and 100 ms STG activity than SZ. In addition to the STG group difference, non-STG activity was also observed in both groups. For example, whereas HC had stronger left and right inferior frontal gyrus activity than SZ, SZ had stronger right superior frontal gyrus and left supramarginal gyrus activity than HC. Conclusions Less STG activity was observed in SZ than HC, indicating encoding problems in SZ. Yet auditory encoding abnormalities are not specific to STG, as group differences were observed in frontal and SMG areas. Thus, present findings indicate that individuals with SZ show abnormalities in multiple nodes of a concurrently activated auditory network.

Frontal slow-wave activity as a predictor of negative symptoms, cognition and functional capacity in schizophrenia

BACKGROUND Increased temporal and frontal slow-wave delta (1-4 Hz) and theta (4-7 Hz) activities are the most consistent resting-state neural abnormalities reported in schizophrenia. The frontal lobe is associated with negative symptoms and cognitive abilities such as attention, with negative symptoms and impaired attention associated with poor functional capacity. AIMS To establish whether frontal dysfunction, as indexed by slowing, would be associated with functional impairments. METHOD Eyes-closed magnetoencephalography data were collected in 41 participants with schizophrenia and 37 healthy controls, and frequency-domain source imaging localised delta and theta activity. RESULTS Elevated delta and theta activity in right frontal and right temporoparietal regions was observed in the schizophrenia v. CONTROL GROUP In schizophrenia, right-frontal delta activity was uniquely associated with negative but not positive symptoms. In the full sample, increased right-frontal delta activity predicted poorer attention and functional capacity. CONCLUSIONS Our findings suggest that treatment-associated decreases in slow-wave activity could be accompanied by improved functional outcome and thus better prognosis.

Antidepressant-induced sweating alleviated by aripiprazole.

To the Editors:As a major cause of medication noncompliance, excessive sweating, or hyperhidrosis, is reported in 5% to 20% of individuals receiving antidepressant therapy.1 Because switching antidepressants often does not resolve sweating, anticholinergic medications are commonly given to reduce sw

Folk and Biological Perceptions of Dementia Among Asian Ethnic Minorities in Hawaii

OBJECTIVE To study if Asian ethnic groups in Hawaii today maintain folk-based beliefs about dementia, have inadequate biomedical understanding of dementia, and differ among each other regarding perceptions of dementia. DESIGN The study adapts and expands a 2004 survey of ethnic groups on perceptions of Alzheimer disease demonstrating that ethnic minority groups hold more folk perceptions and less biomedical perceptions of dementia than Caucasians. This study surveys particular ethnic minority family members of elders admitted to four long-term care and inpatient facilities in Hawaii. Seventy-one family members completed surveys, including 23 Chinese, 18 Filipino, and 30 Japanese participants. Elders may or may not have had the diagnosis of dementia, though an estimated half of elders in all four facilities already held the diagnosis of dementia. RESULTS Findings indicated that Japanese and Chinese respondents in this study held perceptions about dementia that were more consistent with current biomedical understanding compared with their Filipino counterparts (mean differences/percent correct for Japanese: 57%, Chinese: 56% versus Filipino: 38%; F = 6.39, df = 2,55, p = 0.003). Filipino respondents were less likely than Japanese and Chinese respondents to report that persons with dementia can develop physical and mental problems-97% of Japanese participants and 82% of Chinese participants responded correctly compared with 63% of Filipino participants (Fishers Exact test p = 0.009). With regard to folk beliefs about dementia, variation occurred with no consistent trend among the groups. CONCLUSION Low levels of biomedical understanding of dementia were reflected by all three subgroups of Asians living in Hawaii with less prominence of folk beliefs compared with prior studies of ethnic minority perceptions. Education did not predict variability in dementia perceptions among the groups. Lower levels of acculturation, suggested by primary home language other than English, may correlate with a perception of dementia that is less consistent with current biomedical understanding of dementia. Persisting folk beliefs about dementia and the evident lack of biomedical understanding, particularly the belief that dementia is a normal part of aging, emphasizes the need for more culturally tailored strategies in patient education about dementia and the importance of early intervention.

Toxic Effects of Psychotropics Related to Possible P450 Enzyme Inhibition by Kava: Report of 2 Cases

Kava is an herbal remedy popular for centuries among native Pacific Islanders for its sedative effects and use in religious ceremonies. Kava gained popularity in Western countries due to its anxiolytic properties; however, very little is known about potential adverse reactions to kava other than reports of hepatotoxicity. Two cases of patients seen on the psychiatric emergency and consult service who developed severe side effects from psychotropic medications in the context of kava use are presented. In both cases, kava use may have affected the metabolism of the psychotropic medications, leading to serious side effects. Growing research indicates that kava most likely alters concentrations of coadministered psychotropics possibly by inhibiting cytochrome P450 enzymes. This case series highlights the need for greater awareness of safety issues among kava users who also take medications that, when combined with kava, can be life-threatening at toxic levels. Pharmacogenomic testing along with further research about kava and its metabolites could help determine a pharmacologic solution for patients who require psychotropic medications but who would like to preserve cultural traditions and religious practices.

Associations and Heritability of Auditory Encoding, Gray Matter, and Attention in Schizophrenia

BACKGROUND Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). METHODS Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. RESULTS SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function-structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. CONCLUSIONS Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function-structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function-structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function-structure relationships in SZ.

The frequency of hospitalizations and length of stay differences between schizophrenic and schizoaffective disorder inpatients who use cannabis

ABSTRACT Background: The literature on the effects of cannabis use by patients with schizophrenia is variable. Aims: To determine whether there are differences among urine-screened cannabis-only users, polysubstance users using cannabis, and nonusers on the number of inpatient hospitalizations and length of stay for patients with schizophrenia or schizoaffective disorder. Method: This study (N = 116) included patients who tested positive for only cannabis (n = 20, Group 1); tested positive for cannabis and had a history of other substance use (n = 43, Group 2); and had negative drug screens (n = 53, Group 3). Results: Groups 1 and 2 had significantly lower numbers of hospitalizations than Group 3 without controlling for any other factors, and non-significantly lower lengths of stay than Group 3. Conclusions: Our results do not support the hypothesis that cannabis exacerbates psychotic symptoms in patients with schizophrenia or schizoaffective disorder. Our study is unique in that it utilized objective urine drug screens.

Simultaneous usage of dementia medications and anticholinergics among Asians and Pacific Islanders

The simultaneous use of dementia medications and anticholinergic medications occurs frequently. Cholinesterase inhibitors and anticholinergic medications likely counteract one another, potentially exposing patients to medications with decreased benefit, more adverse effects, and higher cost of care. We identified the rate of concurrent prescriptions of cholinesterase inhibitors/memantine with anticholinergics in an urban hospital setting with a large Asian and Pacific Islander population.

Increased Elderly Utilization of Psychiatric Emergency Resources as a Reflection of the Growing Mental Health Crisis Facing Our Aging Population

The elderly population continues to soar in the United States, with the number of those older than 65 years expected to double from 2010 to 2050. Many are predicting an imminent mental health crisis for our seniors, as available resources lag further behind the demand. One contributing factor is the evergrowing number of individuals with dementia-related behavioral symptoms. In Hawaii, a top retirement destination known for longevity of life, we have experienced greater use by elderly patients of the psychiatric emergency department (ED) at the largest general hospital in the state. As evidence of this trend, we present age-specific psychiatric ED utilization patterns from 2007 to 2011, a period during which local resources for geriatric mental health had remained static. We collected data (age, mode of arrival, main diagnosis, length of stay [LOS], and disposition) for all psychiatric ED visits (N = 22,124) in the 5-year period. Patients were grouped as younger (aged <65 years) or older (aged ≥65 years, N = 1,370). Within this period, there was a general trend of more access by elderly patients, with yearly numbers and proportions at 234 (5.7%) in 2007, 220 (5.5%) in 2008, 301 (7.2%) in 2009, 298 (6.2%) in 2010, and 319 (6.5%) in 2011. A more pronounced and alarming progression was seen in law enforcement being increasingly relied upon, usually because of violent behavior, to bring older patients to the ED (12.5% in 2007, 11.0% in 2008, 16.9% in 2009, 18.4% in 2010, and 24.5% in 2011; χ(8) = 41.56, p < 0.01), whereas the numbers of those who arrived by ambulance (64.7%, 50.7%, 59.5%, 59.2%, 54.5%, respectively) or with caregivers/self (22.8%, 38.4%, 23.6%, 22.4%, 21.0%, respectively) trended downward. Behavior due to dementia of all types was recorded as the main presenting diagnosis among 14% of older patients. This number is likely much higher as we were unable to capture secondary diagnoses reliably. Using LOS to estimate ED utilization, older patients had longer LOS (median: 400 minutes) than younger patients (median = 351 minutes, U = 12,362,765, p < 0.01). Among older patients, those receiving medical admission (11% of all elderly visits) had the highest LOS (median: 519 minutes), followed by psychiatric admission (31%, median = 431 minutes) and discharge (58%, median = 352 minutes, KruskalWallis (df 2) = 76.43, p < 0.01; post-hoc medical > psychiatric > discharge). Further, highly advanced age (≥80 years defined as “older old”), compared with “younger old” (aged 65–79 years), was associated with an even greater LOS, but only among those who were psychiatrically admitted (F(2, 1364) = 5.36, p = 0.01, using log-transformed LOS because of positive skew), with the significant interaction term characterized by a median LOS of 457 minutes in “older old” and 409 minutes in “younger old”. Such findings were not surprising. Because of a shortage of geriatric mental health services, exhausted caregivers were often unwilling accept patients back from the ED (usually cases involving the oldest old), where they had to endure lengthy (often multi-day) searches for a limited number of appropriate psychiatric beds. Our observations reflect worrisome outcomes of a fairly stagnant geriatric mental health system, during a period in which growth of the elderly population outpaced other age groups. As a result, symptom acuity and potential for harm rose steadily, as indicated by more law enforcement being invoked by caregivers for transfer to the ED. Lack of acute placement options further worsened crowding in the ED, straining finite acute resources further. Our study period (2007–2011) ushers the very beginning of the baby boomer cohort becoming 65 years or older. Thus, the degree of reliance on ED behavioral services by seniors, especially those with dementia, and their caregivers is likely to increase. Long-term solutions to shore up widening gaps in geriatric mental health are becoming even more urgent.