New structural brain imaging endophenotype in bipolar disorder.

Neuroimaging studies suggest anterior-limbic structural brain abnormalities in patients with bipolar disorder (BD), but few studies have shown these abnormalities in unaffected but genetically liable family members. In this study, we report morphometric correlates of genetic risk for BD using voxel-based morphometry. In 35 BD type I (BD-I) patients, 20 unaffected first-degree relatives (UAR) of BD patients and 40 healthy control subjects underwent 3 T magnetic resonance scanner imaging. Preprocessing of images used DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry in SPM8 (Wellcome Department of Imaging Neuroscience, London, UK). The whole-brain analysis revealed that the gray matter (GM) volumes of the left anterior insula and right inferior frontal gyrus showed a significant main effect of diagnosis. Multiple comparison analysis showed that the BD-I patients and the UAR subjects had smaller left anterior insular GM volumes compared with the healthy subjects, the BD-I patients had smaller right inferior frontal gyrus compared with the healthy subjects. For white matter (WM) volumes, there was a significant main effect of diagnosis for medial frontal gyrus. The UAR subjects had smaller right medial frontal WM volumes compared with the healthy subjects. These findings suggest that morphometric brain abnormalities of the anterior-limbic neural substrate are associated with family history of BD, which may give insight into the pathophysiology of BD, and be a potential candidate as a morphological endophenotype of BD.

Trait impulsivity in patients with mood disorders.

BACKGROUND: Impulsivity is a key component of the manic behavior of bipolar disorder and is reported to occur in bipolar patients as a stable characteristic, i.e. a trait. Nevertheless, impulsivity has not been widely studied in depressed bipolar patients. We assessed impulsivity in depressed and euthymic bipolar and unipolar patients and healthy controls. We hypothesized that bipolar subjects would have higher levels of trait impulsivity than the comparison groups. METHODS: Twenty-four depressed bipolar, 24 depressed unipolar, 12 euthymic bipolar, and 10 euthymic unipolar patients, as well as 51 healthy subjects were evaluated with the Barratt Impulsiveness Scale (BIS). Analysis of covariance with age and sex as covariates was used to compare mean group differences. RESULTS: Depressed bipolar, euthymic bipolar, and depressed unipolar patients did not differ, and showed greater impulsivity than healthy controls on all of the BIS scales. Euthymic unipolar patients scored higher than healthy controls only on motor impulsivity. LIMITATIONS: Higher number of past substance abusers in the bipolar groups, and no control for anxiety and personality disorders, as well as small sample sizes, limit the reach of this study. CONCLUSIONS: This study replicates prior findings of stable trait impulsivity in bipolar disorder patients, and extends them, confirming that this trait can be demonstrated in depressed patients, as well as manic and euthymic ones. Trait impulsivity may be the result of repeated mood episodes or be present prior to their onset, either way it would influence the clinical presentation of bipolar disorder.

Multi-center randomized clinical trials in oral and maxillofacial surgery: modeling of fixed and random effects.

The multi-center randomized clinical trial (MCCT) is an important tool to evaluate treatment of rare diseases. An important and challenging analytic consideration is how to model the variability of the set of clinical centers composing an MCCT. The purpose of this paper was to demonstrate how changing the assumptions regarding the variability (fixed effect versus random effect) of the set of clinical centers may alter the results. The data for this paper were derived from a recently completed MCCT. The MCCT was designed as a prospective, randomized clinical trial comparing the stability of two techniques, i.e., wire versus rigid internal fixation (RIF), for stabilizing the mandible after bilateral sagittal split ramus osteotomy (BSSO) for patients requiring mandibular advancement. Three treatment centers were involved. The key outcome variable was change in mandibular position (B-point) over time. We developed two different analytic models by varying the underlying statistical assumptions regarding the variability of the clinical treatment centers, i.e., random or fixed effects. Analyses based on the random-effects model demonstrated no significant difference between treatment groups in terms of relapse (P=0.13). With the fixed-effects model, however, wire fixation had significantly more relapse at B-point over time than RIF (P=0.02). The results from these two sets of analyses demonstrate how changing assumptions regarding the variability of the set of clinical centers can alter the interpretation of the treatment effect. The choice of statistical modeling of the set of clinical centers is an important consideration when performing analyses of MCCTs and it is a decision that should be made prior to initiating the study.

Factors affecting amnesia, seizure duration, and efficacy in ECT.

Twenty-nine patients given unilateral ECT were tested for memory with each treatment. Forgetting of nonverbal material correlated positively with seizure duration and with anesthetic dose. Seizure duration did not correlate with forgetting of verbal material or with changes in Hamilton depression ratings. Seizure duration was inversely related to succinylcholine and methohexital doses. These findings suggest that muscle relaxant and anesthetic doses can be adjusted to lessen the amnestic effects of ECT. There are, however, insufficient data on the relationship between seizure length and ECT efficacy to specify a minimum duration for seizures, individually or cumulatively.

Endocrine, psychological and genital response to sexual arousal in men.

The endocrine, genital, and cognitive--affective responses of sexually functional men were compared under sexually arousing and non-arousing conditions. Sexually aroused subjects showed significantly higher serum luteinizing hormone concentrations than non-aroused subjects. Testosterone concentration was correlated with higher levels of penile response, but it did not prime further sexual arousal. Cortisol and prolactin concentrations decreased in both groups, more in the non-aroused group, and appeared to both inhibit and facilitate sexual response, depending on the level of anxiety reported by the subjects. Cortisol was correlated with self-reported worry, and testosterone with relaxation. These results support a multidimensional approach to the endocrine study of sexual arousal that includes both cognitive and genital response components.

Cutaneous vascular and sudomotor responses to isometric exercise in humans.

To identify whether isometric handgrip exercise (IHG) affects cutaneous vasoconstrictor and/or active vasodilator activities, seven subjects (6 men and 1 woman) performed 30% maximal voluntary contraction of a forearm under normothermic (1 bout) and hyperthermic (2 bouts) conditions. Skin blood flow was indexed by laser-Doppler flowmetry at a contralateral forearm site at which adrenergic vasoconstrictor function was blocked by iontophoresis of bretylium tosylate (BT) and therefore only has active vasodilation as a mechanism for reflex control. Skin blood flow was also monitored at an adjacent untreated site. Cutaneous vascular conductance (CVC) was calculated from the flow signal and noninvasive blood pressure. CVC was normalized to the value obtained from maximal vasodilation at that site. Sweat rate (SR) was measured at the same locations. During normothermia, IHG did not affect CVC at the control or BT-treated sites, nor did IHG affect SR (P > 0.05). The second bout of IHG in hyperthermia evoked significant reductions in CVC at the untreated (69.4 +/- 3.4 to 58.9 +/- 2.5% of maximum, P < 0.05) and BT-treated sites (75.4 +/- 6.1 to 64.4 +/- 6.2% of maximum, P < 0.05), whereas SR significantly increased (0.62 +/- 0.16 to 0.70 +/- 0.17 mg.cm-2.min-1, P < 0.05). These findings uniquely show that, in hyperthermia, IHG reduces active vasodilator activity while at the same time sudomotor activity is increasing. This suggests independent control of these effectors.

Association of salivary flow rates with maximal bite force.

Mean salivary secretion and bite force decrease with advancing age. Previous studies have shown that salivary flow rates are influenced by mastication. In the present study, we examined the relationship between salivary flow rates and maximal bite force in a community-based sample of men and women 35 years of age or older. Salivary flow rates for unstimulated whole and unstimulated submandibular/sublingual (SMSL) saliva as well as citrate-stimulated parotid and SMSL saliva were measured in 399 subjects. Bite force was assessed with a bilateral force transducer. Pearson correlation analysis yielded significant positive correlations between bite force and flow rates for unstimulated whole saliva (r = 0.24, p < 0.0001), stimulated parotid saliva (r = 0.13, p < 0.03), unstimulated SMSL (r = 0.14, p < 0.0001), and stimulated SMSL (r = 0.16, p < 0.003). When adjusted for age and gender, the partial correlations between bite force and salivary flow rates remained significant for unstimulated whole saliva (r = 0.10, p < 0.05), stimulated parotid saliva (r = 0.13, p < 0.02), and stimulated SMSL saliva (r = 0.14, p < 0.006). Subjects were divided into four groups based on their maximal bite force score (low, medium low, medium high, and high). For each saliva type, the flow rate of the high-bite-force group was significantly greater than that of the low-bite-force group as well as that of the medium-high-bite-force group. These results confirm an age-related decrease in bite force and salivary flow rates and show that, regardless of age or gender, bite force is correlated with salivary flow.

Oral function and diet quality in a community-based sample.

Overall diet quality indices, such as the Healthy Eating Index (HEI), are preferred for epidemiological studies, yet studies in dentistry have focused on isolated dietary components. This study investigated the influence of socio-demographic and masticatory variables (masticatory performance, bite force, number of posterior functional tooth units, TMJ disorder, and dentition status) on overall diet quality in a community-based sample (n = 731). Cross-sectional data were derived from clinical examinations, bite force recordings, masticatory performance measurements, and two 24-hour dietary recalls. Females, European-Americans, and older subjects had better HEI scores than males, Mexican-Americans, and younger subjects, respectively. Income, education, and the masticatory variables were not related to diet quality. Analyses according to dentition status (good dentition, compromised dentition, partial denture, and complete dentures) showed no inter-group differences for HEI except for the age groups. The results suggest that the chewing-related factors evaluated in this sample are not predictors of overall diet quality across the socio-demographic groups.

Determinants of masticatory performance in dentate adults.

Masticatory performance results from a complex interplay of direct and indirect effects, yet most studies employ univariate models. This study tested a multivariate model of masticatory performance for dentate subjects. Explanatory variables included number of functional tooth units, bite force, sex, age, masseter cross-sectional area, presence of temporomandibular disorders, and presence of diabetes mellitus. The population-based sample consisted of 631 dentate subjects aged 37-80 years. Covariance structure analysis showed that 68% of the variability in masticatory performance could be explained by the combined effects of the explanatory variables. Age and sex did not show a strong effect on masticatory performance, either directly or indirectly through masseter cross-sectional area, temporomandibular disorders, and bite force. Number of functional tooth units and bite force were confirmed as the key determinants of masticatory performance, which suggests that their maintenance may be of major importance for promoting healthful functional status.

Effect of experimental stress on masseter and temporalis muscle activity in human subjects with temporomandibular disorders.

Temporomandibular (TM) disorders have an uncertain aetiology. The purpose of this study was to replicate and extend the work of Yemm (1969) (Archs oral Biol. 14, 873-878, 1437-1439; Br. dent. J. 127, 508-510), who reported a lack of habituation to experimentally induced stress in subjects with TM disorders. In this study, 20 TM disorder patients and 20 controls, matched for age and sex, performed a timed psychomotor task while bilateral masseter and anterior temporalis electromyographic (EMG) activity, finger temperature and skin admittance were monitored. These data were sampled, stored every 4s and averaged by an Apple II Plus/ISAAC interface. A significant trials effect for finger temperature (F[4/152] = 34.99, p less than 0.001) and skin admittance (F[4/152] = 41.90, p less than 0.001) was found, suggesting that the independent variable (stress) had been successfully manipulated. A significant trials by groups effect was found for right temporalis EMG activity (F[3/144] = 3.94, p less than 0.05); the left temporalis showed a similar, but not significant, trend. The masseter muscles did not show differences or trends between groups. No significant differences were found in resting EMG levels or in the initial magnitude of EMG responses during baseline. These results provide support for the hypothesis that TM disorder and control groups respond differently to stress in terms of habituation to stressful stimuli.

The effects of severe bruxism on sleep architecture: a preliminary report.

Analysis of sleep in 5 severe bruxists revealed consistent sleep abnormalities. These abnormalities consisted of decreased REM latency (90%), decreased percentage of REM sleep (85%), and increased number of sleep stage transitions (75%). This sleep pattern suggests that bruxing can have a deleterious effect on sleep in otherwise healthy individuals. This effect on sleep can in the long run lead to difficulty in daytime functioning similar to the effects of sleep apnea or nocturnal myoclonus. These data also reveal a significant first night effect, hence future attempts at replicating and expanding these findings should take that into consideration. The small number of subjects studied, the lack of a standardized assessment of their daytime functioning, the lack of information regarding the degree of teethware and daytime bruxing activity limit the generalizability of our findings. A controlled study with a larger sample size can help further delineate the nature of such sleep changes as well as their impact on the patient's overall functioning.

Effects of major Class II occlusal corrections on temporomandibular signs and symptoms.

This study explored the relationship between malocclusion and signs and symptoms of temporomandibular disorders (TMD) in 124 patients with severe Class II malocclusion, before and 2 years after bilateral sagittal split osteotomy (BSSO). Patients were evaluated with the Craniomandibular Index (CMI), the Peer Assessment Rating Index (PAR Index, to assess gross changes in the occlusion), and symptom questionnaires. The results showed a significant improvement in occlusion; PAR Index scores dropped from a mean of 18.1 before surgery to a mean of 6.1 at 2 years postsurgery (P < 0.001). The CMI and masticatory index (MI) for muscle pain indicated clinically small but statistically significant improvement (P = 0.0001) from before surgery (mean CMI = 0.14, mean MI = 0.15) to after surgery (mean CMI = 0.10, mean MI = 0.08). The number of patients with clicking upon opening decreased significantly from 33 (26.6%) to 13 (10.5%) (P = 0.001). However, the number of patients with fine crepitus increased from 5 (4.0%) before surgery to 16 (12.9%) at 2 years postsurgery (P = 0.005). Significant reductions in subjective pain and discomfort were also found 2 years after surgery. The magnitude of change in muscular pain was not related to the severity of the pretreatment malocclusion, a finding that suggests that factors other than malocclusion may be responsible for the change in TMD.

Classical conditioning in children with attention deficit hyperactivity disorder (ADHD) and anxiety disorders: a test of Quay's model.

Quay (1988) put forward a model of childhood mental disorders based on Gray's (1982) theory that there exists within the brain a behavioral inhibition system (BIS), which processes signals related to aversive or punishing stimuli. According to this model, children with attention deficit hyperactivity disorder (ADHD) show lower than optimal levels of activity in this system, which leads to less responsiveness at a physiological level to signals related to punishment. Children with ADHD and controls were compared on a classical conditioning paradigm. Skin conductance and cardiac responses were measured in response to a conditioned stimulus that had been paired with an aversive unconditioned stimulus. There were no differences between the groups, suggesting that, in terms of classical conditioning, ADHD children are equally responsive to signals related to punishment as controls.

Mandibular range of motion after bilateral sagittal split ramus osteotomy with wire osteosynthesis or rigid fixation.

OBJECTIVES: An analysis was conducted to compare mandibular range of motion among Class II patients treated with wire osteosynthesis or rigid internal fixation after surgical mandibular advancement. STUDY DESIGN: Patients randomly received wire osteosynthesis and 8 weeks of maxillomandibular fixation (n = 49) or rigid internal fixation (n = 78). Mandibular range of motion was measured 2 weeks before surgery and 8 weeks, 6 months, and 1, 2, and 5 years after surgery. RESULTS: Both groups showed decreased mobility in all movement dimensions that progressively recovered to near presurgical levels over the 5-year follow-up period. The difference in range of motion between treatment groups was not statistically significant. Changes in proximal and distal segment position could not explain decreased mobility. CONCLUSIONS: Similar decreases in mandibular mobility occurred with wire and rigid fixation of a bilateral sagittal split ramus osteotomy after surgery. Long-term changes were statistically, but not clinically, significant.

Bilateral sagittal split osteotomy and temporomandibular disorders: rigid fixation versus wire fixation.

OBJECTIVE: The effects of orthognathic surgery on temporomandibular disorders may be related to the surgical method that is used. Specifically, it has been suggested that the choice of stabilization technique may play a major role in the functional outcome of mandibular advancement surgery. The purpose of this study was to prospectively compare long-term (2 years) signs and symptoms of temporomandibular disorders after orthognathic surgery with bilateral sagittal split osteotomy in 127 patients randomized to receive rigid or wire fixation. STUDY DESIGN: Signs and symptoms of temporomandibular disorders were evaluated before and 2 years after surgery by means of the overall craniomandibular index (CMI), dysfunction index (DI), and muscle index (MI). Patients also reported subjective symptoms of temporomandibular disorders by marking areas of pain on a standard drawing of the head and rating the pain in each area on a scale ranging from 1 (very mild) to 7 (very extreme). Subjective pain was also assessed through use of the Oral Health Status Questionnaire and by a rating of the difficulty in opening the mouth because of pain. RESULTS: There were no statistically significant differences in the CMI, MI, or DI change scores between the wire and rigid fixation groups (mean CMI(wire) = 0.05, mean CMI(rigid) = 0.04; mean DI(wire) = 0.02, mean DI(rigid) = 0. 01; mean MI(wire) = 0.08, mean MI(rigid) = 0.08) 2 years after surgery. Temporomandibular joint sounds also demonstrated no significant differences between the two fixation methods. Subjective pain reports were consistent with the clinical examinations. On average, both wire and rigid scores decreased slightly, but the change scores were not significantly different between groups. CONCLUSIONS: These findings suggest that the long-term (2 years) effects of wire and rigid internal fixation methods on the signs and symptoms of temporomandibular disorders do not differ. Earlier concerns about increased risk for temporomandibular disorders with rigid fixation were not supported by these results.

Is use of exogenous estrogen associated with temporomandibular signs and symptoms?

BACKGROUND: Studies of historical data suggest a link between exogenous estrogen use and referral for treatment for temporomandibular disorders, or TMDs. The purpose of the authors' study was to determine the association between exogenous estrogen use and signs and symptoms of TMD assessed by direct physical examination in a randomly selected community sample of primarily postmenopausal women. METHODS: A calibrated clinical examiner examined a stratified random sample of 510 women aged 37 to 82 years using the Craniomandibular Index, or CMI. All medications that subjects were taking at the time of the examination were identified by interview and examination of subjects' medication containers on two occasions. One hundred seventy-four subjects were taking medications containing estrogen, and 336 were taking no such medications. RESULTS: The muscle and joint signs and symptoms of women taking and not taking estrogen were not significantly different after the authors controlled for sociocultural, demographic and health care utilization variables. Estrogen use also failed to distinguish women receiving relatively high and low scores on the CMI. CONCLUSION: Estrogen replacement therapy does not place women at increased risk of developing TMDs. CLINICAL IMPLICATIONS: Clinicians need not be concerned that patients taking oral contraceptives or replacement estrogens are at increased risk of developing TMDs.

Comparing prospective and retrospective evaluations of temporomandibular disorders after orthognathic surgery.

The authors conducted a study to document agreement between prospective examinations performed by trained clinical trial examiners and retrospective surgical chart reviews in identifying signs and symptoms of temporomandibular disorders, or TMD. Only a small fraction of the signs and symptoms identified by clinical trial examiners were documented in the surgical charts. Studies relying on retrospective chart reviews may seriously underestimate signs and symptoms of TMD.

Sequential combination of self-report, breath carbon monoxide, and saliva cotinine to assess smoking status.

The purpose of this analysis was to develop an algorithm for the cost effective and accurate assessment of smoking during the previous few days by combining self-report, breath carbon monoxide (BCO), and saliva cotinine (sCOT). These measurements are convenient, quantitative, and do not require invasive procedures. The data used to devise the algorithm were gathered during a treatment trial of participants seeking to stop smoking. Self-report of smoking was determined using a written questionnaire, BCO was measured with a handheld breathalyzer, and sCOT was quantified using a high sensitivity ELISA. Participants were 130 males and 97 females between the ages of 19 and 67 years who reported smoking at least 15 cigarettes a day and had a BCO level ≥ 15 ppm. Self-reports and BCO levels were collected at each of 6 visits (V0-V5) and sCOT levels were determined at V0 and V5. Based on the data collected, we recommend that the sequential determination of self-reported smoking, BCO level, and sCOT level be employed to assess smoking during the previous few days to minimize the higher cost and longer turnaround time associated with the sCOT test while maximizing accuracy.