Persistent infection with neurotropic herpes viruses and cognitive impairment.

BACKGROUND: Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n=1852). Method Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens. RESULTS: PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 × 10-5 and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (ß = -0.25, p = 7.28 × 10-10). There were no significant interactions between exposure and group status. CONCLUSIONS: Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status.

Linkage analysis of schizophrenia in African-American families.

While many studies have sought a window into the genetics of schizophrenia, few have focused on African-American families. An exception is the Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS), which seeks to identify novel and known risk variation for schizophrenia by genetic analyses of African-American families. We report a linkage study of diagnostic status in 217 African-American families using the Illumina Linkage Panel. Due to assumed incomplete and time-dependent penetrance, we performed linkage analysis using two different treatments of diagnosis: (1) treating both affected and unaffected individuals as informative for linkage (using the program SIBPAL) and (2) treating only affected individuals as informative (using the program MERLIN). We also explore three definitions of affected status: narrowly defined schizophrenia; one broadened to include schizoaffective disorder; and another including all diagnoses indicating psychosis. Several regions show a decrease in the evidence for linkage as the definition broadens 8q22.1 (rs911, 99.26 cM; SIBPAL p-value [p] goes from 0.006 to 0.02), 16q24.3 (rs1006547, 130.48 cM; p from 0.00095 to 0.0085), and 20q13.2 (rs1022689, 81.73 cM; p from 0.00015 to 0.032). One region shows a substantial increase in evidence for linkage, 11p15.2 (rs722317, 24.27 cM; p from 0.0022 to 0.0000003); MERLIN results support the significance of the SIBPAL results (p=0.00001). Our linkage results overlap two broad, previously-reported linkage regions: 8p23.3-p12 found in studies sampling largely families of European ancestry; and 11p11.2-q22.3 reported by a study of African-American families. These results should prove quite useful for uncovering loci affecting risk for schizophrenia.

Manic syndrome after metrizamide myelography.

Depression, anxiety, and delirium have been associated with metrizamide myelography. The authors report a patient who developed an organic affective disorder with manic symptoms several hours after metrizamide myelography.

Benefit of nasal CPAP in obstructive sleep apnea is due to positive pharyngeal pressure.

The purpose of this study was to determine if the mechanism of nasal continuous positive airway pressure's (CPAP's) effectiveness is to act as a pneumatic splint or to increase functional residual capacity (FRC) and consequently, upper airway caliber. Four subjects with obstructive sleep apnea underwent 3 nights of polysomnography: night 1, control; night 2, nasal CPAP; night 3, external subatmospheric pressure (ESAP). ESAP, a negative pressure body suit, increases FRC. We measured the changes in FRC with nasal CPAP and ESAP using the weighted spirometer technique. The dose used for the ESAP night was the dose that produced the same FRC as the subject's prescribed nasal CPAP dose. The mean number of arousals and the respiratory events index were higher on ESAP and control nights. Less severe oxygen desaturation occurred during non-rapid-eye-movement sleep on the nasal CPAP and ESAP nights. These preliminary results show that increasing FRC alone does not account for the effectiveness of nasal CPAP, and splinting of the collapsible upper airway is necessary.

Interviewing with intravenous drugs.

Drug assisted interviewing is of demonstrated value in differentiating organic from functional delirious states. Its role in the differential diagnosis of major mental illness is unclear; but well-timed interviews may provide useful additional data. Unfortunately the data is usually difficult to interpret. It certain forms of amnesia, drug assisted interviewing may facilitate retrieval of otherwise unavailable memories, yet these memories are no more reliable than those obtained in conventional interviews. The use of intravenous drugs in psychotherapy has generated encouraging reports which have not, however, been subjected to controlled study. The use of drug interviews, similar to hypnosis, in the treatment of intractable conversion has been long known in clinical practice. The long-term benefit of such interventions is not known. Drug-assisted interviewing has a long, if controversial, history in clinical psychiatry. Its limitations and usefulness are often misunderstood. In addition, there is a deficit of well-controlled study of drug-assisted interviewing. Nevertheless, well-timed interviews, employing properly executed technique, may be helpful in a range of diagnostic and therapeutic situations.

Shy-Drager syndrome presenting as depression: case report.

A case of Shy-Drager syndrome (proven at autopsy) initially presented as a depressive disorder. Shy-Drager syndrome should be added to the list of subcortical neurologic disorders which may initially present with an affective disturbance.

Gastric surgery for respiratory insufficiency of obesity.

Morbid obesity is often associated with severe respiratory insufficiency, commonly known as the pickwickian syndrome. This can be divided into the following two primary breathing disorders which can affect patients alone or in combination: the obstructive sleep apnea syndrome (SAS); and the obesity-hypoventilation syndrome (OHS). Thirty-eight (14 percent) of 263 morbidly obese patients with respiratory insufficiency of obesity underwent gastric surgery for weight reduction. Ten had OHS, nine has SAS, and 19 had both. Of these patients, one died of postoperative complications, one died at five weeks with an inconclusive autopsy, one was lost to follow-up, and the time since surgery was too short (less than three months) in three. A total of 30 patients lost 45 +/- 25 percent (p less than 0.0001) of excess body weight within 3 to 12 months following surgery, when repeat pulmonary studies were done. Most patients continued to lose additional weight until two years, when they had lost 62 +/- 26 percent of excess weight. Nine patients failed initial surgery (gastroplasty); seven of these were successfully converted to gastric bypass. Weight loss was associated with a significant decrease in the percentage of sleep apnea from 44 +/- 15 to 8 +/- 11 (p less than 0.0001). In patients with OHS, the arterial oxygen pressure (PaO2) increased from 53 +/- 9 to 68 +/- 11 mm Hg (p less than 0.0001), and the arterial carbon dioxide tension decreased from 51 +/- 7 to 41 +/- 4 mm Hg (p less than 0.0001). Pulmonary function tests in the patients with OHS revealed significant increases, as a percentage of predicted normal, in the forced vital capacity, forced expiratory volume in one second, expiratory reserve volume, functional residual capacity, and total lung capacity. Secondary polycythemia, defined as a hemoglobin level greater than 16 g/dl associated with a PaO2 less than 60 mm Hg, was noted in 13 of 29 patients with OHS. This fell from 16.9 +/- 1.1 to 14.9 +/- 1.7 g/dl (p less than 0.001) after weight loss and improved pulmonary function.

Effects of protriptyline on vigilance and information processing in narcolepsy.

Vigilance, memory function, and response latency on the Sternberg short-term memory scanning task were examined in eight narcoleptic patients on and off medication. Off medication, half of the patients demonstrated reduced vigilance and all displayed diminished automatic memory encoding and longer response latencies on the Sternberg memory scanning procedure relative to the treated condition. Protriptyline normalized vigilance in half of the patients, while response latency and automatic information processing significantly improved in all. These findings are discussed with regard to the potential effect of the medication on central nervous system arousal.

Selective reminding procedure in depression and dementia.

Patients with mild dementia of the Alzheimer's type (DAT), patients with major depression, and normal elderly control subjects were administered a verbal learning task using the selective reminding procedure. Depressed patients were impaired on total recall and the proportion of items retained from one trial to the next without reminding and did not benefit from imagery in retaining items over consecutive trials. The DAT patients were impaired on all measures derived from the test, including storage and recognition memory. With the exception of the ability to benefit from imagery, all of the measures distinguished depressed and mild DAT patients. These findings are consistent with deficient encoding in DAT and performance deficits as a function of effortful cognitive processing in depression.

Productive naming and memory in depression and Alzheimer's type dementia.

Patients with mild to moderate dementia of the Alzheimer's type (DAT), patients with major depression, and normal controls completed tests of productive naming and verbal recall memory. Both depressed and DAT patients demonstrated reduced verbal fluency on productive naming tasks, indicating limited utility of such tasks in differential diagnosis. There was a stronger relationship between verbal fluency and memory in DAT patients than in depressed patients. The linguistic component as well as the requirement for cognitive speed may be important in explaining the deficit of DAT patients on productive naming tasks. In contrast, the speed component may be particularly important for depressed patients whose poor performance may reflect a motivational deficit.

Current concepts of geriatric pain and its treatment.

Because stress and depression are prevalent in the elderly, the opportunity for pain to intensify stress and depression may be greater in older people than in the general population. Evidence that pain-related psychosomatic complaints are more frequent in the elderly further complicates the issue. Antidepressants that affect serotonergic systems may have analgesic properties independent of their antidepressant properties; eg, amitriptyline and doxepin. These drugs may have a more rapid effect on pain than on depression.

A six month randomized controlled trial of long acting injectable risperidone 50 and 100mg in treatment resistant schizophrenia.

It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100mg, would be more effective than RLAI, 50mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone+9-hydroxyrisperidone, during treatment with RLAI 100mg, were comparable to those for 6-8 mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥ 50-100mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥ six months.

Heritability of functioning in families with schizophrenia in relation to neurocognition.

UNLABELLED: The role of daily functioning is an integral part of the schizophrenia (SZ) phenotype and deficits in this trait appear to be present in both affected persons and some unaffected relatives; hence we have examined its heritability in our cohort of African American schizophrenia families. There is now ample evidence that deficits in cognitive function can impact family members who are not themselves diagnosed with SZ; there is some, but less evidence that role function behaves likewise. We evaluate whether role function tends to "run in families" who were ascertained because they contain an African American proband diagnosed with SZ. METHODS: We analyzed heritability for selected traits related to daily function, employment, living situation, marital status, and Global Assessment Scale (GAS) score; modeling age, gender, along with neurocognition and diagnosis as covariates in a family based African-American sample (N=2488 individuals including 979 probands). RESULTS: Measures of role function were heritable in models including neurocognitive domains and factor analytically derived neurocognitive summary scores and demographics as covariates; the most heritable estimate was obtained from the current GAS scores (h2=0.72). Neurocognition was not a significant contributor to heritability of role function. CONCLUSIONS: Commonly assessed demographic and clinical indicators of functioning are heritable with a global rating of functioning being the most heritable. Measures of neurocognition had little impact on heritability of functioning overall. The family covariance for functioning, reflected in its heritability, supports the concept that interventions at the family level, such as evidenced-based family psychoeducation may be beneficial in schizophrenia.