Menstrual cycle-related brain metabolite changes using 1H magnetic resonance spectroscopy in premenopausal women: a pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) was used to assess neurochemical brain changes across the menstrual cycle in five women with premenstrual dysphoric disorder (PMDD) and six control subjects. Women with PMDD and control subjects were scanned on days 8 and 26 within one menstrual cycle (i.e. at times of complete absence and height of PMDD symptoms, respectively). The point resolved spectroscopic sequence (PRESS) was used to localize a voxel of 8 ml in the medial frontal gray matter and in the occipito-parietal white matter. The ratio of N-acetyl-aspartate to creatine in the region of the medial prefrontal cortex and the cingulate gyrus declined significantly from the follicular to the luteal phase in both groups of subjects. The menstrual phase-dependent significant increase in the ratio of choline to creatine was observed in the parietal white matter. The myo-inositol/creatine ratio exhibited a trend toward higher levels in the PMDD patients in the luteal phase of the menstrual cycle. Differences between PMDD and control subjects were not statistically significant. Menstrual cycle phase-dependent changes in ovarian hormonal concentrations may influence the neurochemistry of brain activity in premenopausal women.

Clinical correlation of neuropsychological tests with 1H magnetic resonance spectroscopy in hepatic encephalopathy.

OBJECTIVE: The purpose of this project was to correlate neuropsychological test results with in vivo measures of regional cerebral biochemistry determined by 1H MRS in patients with subclinical and mild hepatic encephalopathy. METHODS: Baseline 1H MRS scans and neuropsychological testing of patients occurred at entry into the study. The primary localized volume chosen for the 1H MRS study was the posteromedial parietal cortex, which consisted predominantly of white matter. Some of these patients were scanned again if they received a liver transplantation. In a subset of patients, the effect on cerebral biochemistry and neuropsychological test performance due to a dietary intervention of reduced protein intake was monitored. These patients underwent a baseline examination and a repeat examination after 2 weeks of dietary intervention. Measures were made of the correlation between the dietary intervention and 1H MRS determined biochemistry and the results of neuropsychological tests. Results in both patient groups (dietary intervention and no dietary intervention) were compared with healthy control subjects. RESULTS: Subclinical and low grade HE patients showed a significant reduction in mI/Cr and Cho/Cr ratio when compared with healthy control subjects. These patients also showed impairment in frontal lobe mediated cognitive tasks and in motor ability that were not appreciated in a bedside examination. The patients did not return to normal cerebral metabolic states within 30 to 60 days of liver transplantation. In fact, reductions remained in mI/Cr. Cho/Cr values increased after transplantation compared with healthy control subjects. CONCLUSIONS: 1H MRS studies showed changes in regional cerebral biochemistry associated with all grades of HE. There was a reduction in mI/Cr and a reduction in Cho/Cr in patients with low grade and subclinical forms of HE compared with normal subjects. The reduction in mI correlated well with abnormalities observed in neuropsychological tests. Liver transplantation was not associated with significant improvement in these variables.

Electroconvulsive therapy increases circadian amplitude and lowers core body temperature in depressed subjects.

BACKGROUND: Reduced amplitude of the circadian temperature rhythm and elevated nocturnal body temperature normalize after successful pharmacotherapy of major depression. METHODS: Core body temperature was continually monitored in three groups: a) 6 depressed patients before an electroconvulsive therapy (ECT) course and b) after an ECT course; and c) 6 healthy, sex-matched controls of similar age. RESULTS: The 24-hour profile of temperature was significantly different in patients pre-ECT than in patients post-ECT or in controls. Post-ECT subjects and controls manifested 24-hour profiles similar to one another. Circadian temperature rhythm amplitude increased after ECT. The mean asleep and mean 24-hour temperatures were significantly higher in patients pre-ECT than post-ECT and controls. CONCLUSIONS: We find that ECT restores a disrupted circadian temperature rhythm in depressed patients.

Databases for clinical psychiatry.

Clinical information systems support patient care and research while providing data for administrative use. We assessed the informational needs of the psychiatrists at UCLA Neuropsychiatric Hospital and used the resulting criteria in evaluating commercial computer products. The systems that appear to be least expensive, most powerful, and most suitable for widespread use are assembled from various off-the-shelf packages. These newer systems use a structured query language (SQL) database with a graphic user interface. An SQL database can support both large and small clinical operations, and a graphic interface is easy to use. Commercial software systems are too expensive for a small psychiatric hospital or department, but a customized SQL database can be purchased and installed at lower cost.

Selective serotonin reuptake inhibitors. Assessment for formulary inclusion.

Depression is a common and significant health problem associated with impairment in a patient's ability to function in their role (e.g. student, worker, home-maker), and may have a fatal outcome in the case of suicide. Recently there has been progress in developing new antidepressant medications, such as the selective serotonin reuptake inhibitors (SSRIs). These agents, while no more effective than the tricyclic antidepressant (TCA) drugs, are generally better tolerated than traditional medications used to treat depression. Further, because of their adverse effect profiles, they are generally better tolerated, and safer in overdose, than the TCAs. In response to concerns about aggregate healthcare costs, formularies are being employed to control the direct costs of prescription drugs. When direct drug costs alone are considered, the TCAs are initially less expensive than the SSRIs. However, compared with those taking SSRIs, patients taking TCAs withdraw from treatment more frequently, have more accidents, experience more adverse effects that require treatment, and are more likely to die from an overdose (if it occurs). Furthermore, unsuccessful treatment may be due to noncompliance, which is frequently related to adverse effects. Medications have effects on indirect costs. For example, adverse effects may impair productivity and lead to accidents in the home and at work. There are increased hospital and indirect costs of drugs used in overdose. Medication non-compliance may lead to failure to recover from depression, which results in ongoing expense to the state in the form of disability benefit payments. The largest cost savings are often associated with indirect costs, such as reduced benefit payments and improved productivity and earnings when treatment is successful. Taking all these considerations together, it does not appear that TCAs, taken over time, are any less expensive than the newer antidepressant medications.

Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study.

Early morning sleep deprivation (patient awake from 0200 to 2200 hours) produces a same-day antidepressant effect in approximately one-half of patients with major depression. Unfortunately, these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours. Recent work suggests, however, that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinically useful. In a 30-day study, we compared the abilities of four different treatments (lithium plus early morning sleep deprivation, lithium plus a control sleep deprivation procedure, and desipramine with either of the two sleep manipulations) to induce a rapid (next-day) and sustained antidepressant response in 16 depressed patients. Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation, and the response was sustained for at least 30 days. In this design, however, lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission. These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted.

The neuropathologic basis of major affective disorders: neuroanatomic insights.

Attempts to elucidate the pathophysiology of symptom production in mood disorders can be enhanced by information from two sources. First, insights into localization can be gained from the secondary mood disorders; these clinical problems suggest the brain regions that, when altered, are associated with specific symptoms. Second, both structural and functional brain imaging suggest specific regions where abnormalities are associated with mood disorders. Data that emerge from these sources implicate the basal ganglia, frontal cortex, and temporal lobes in the production of mood disorder symptoms. However, the specific neuroanatomic subregions involved and the associated biochemical changes await full elucidation.

New antidepressants and the treatment of depression.

Depression is a common and significant health problem associated with impairment in a patient's ability to function. The development of new antidepressant medications represents progress in its treatment. These new agents work through the selective blockade of the reuptake of serotonin into the presynaptic neuron, thereby increasing the availability of this neurotransmitter at the synaptic cleft and enhancing its effectiveness. While no more effective than traditional tricyclic antidepressant drugs, the new agents are generally safer than traditional medications used to treat depression: they are well tolerated and, in case of overdose, less harmful than tricyclic antidepressants.

Leukoencephalopathy and major depression: a preliminary report.

The comparative prevalence of leukoencephalopathic changes in 119 young and old inpatients and outpatients with major depression was examined. Patients underwent magnetic resonance imaging (MRI) examinations with T1- and T2-weighted pulse sequences. Leukoencephalopathic changes were uncommon in depressed patients and medical control subjects younger than 45 years of age. Such changes were, however, seen in approximately 44% of older depressed patients and 30% of elderly medical control subjects.

Reliability of drawing regions of interest for positron emission tomographic data.

We determined interrater reliability for two raters who independently used a standard protocol to draw regions of interest (ROIs) on F-18 fluorodeoxyglucose positron emission tomographic data acquired from eight patients with mild to moderate memory impairment. Intraclass correlation coefficients for region sizes (total pixel number) varied among anatomical ROIs (RIs from 0.324 to 0.935). However, correlations calculated from relative metabolic rates (normalized average counts) were consistently high (RI > or = 0.954). The raters also showed high agreement for region recognition on each image plan (kappa = 0.978). These results suggest that rater disagreements in ROI margins have minimal impact on average count densities used to calculate metabolic rates.

Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder.

We used positron emission tomography to investigate local cerebral metabolic rates for glucose (LCMRG1c) in patients with obsessive-compulsive disorder before and after treatment with either fluoxetine hydrochloride or behavior therapy. After treatment, LCMRG1c in the head of the right caudate nucleus, divided by that in the ipsilateral hemisphere (Cd/hem), was decreased significantly compared with pretreatment values in responders to both drug and behavior therapy. These decreases in responders were also significantly greater than right Cd/hem changes in nonresponders and normal controls, in both of whom values did not change from baseline. Percentage change in obsessive-compulsive disorder symptom ratings correlated significantly with the percent of right Cd/hem change with drug therapy and there was a trend to significance for this same correlation with behavior therapy. By lumping all responders to either treatment, right orbital cortex/hem was significantly correlated with ipsilateral Cd/hem and thalamus/hem before treatment but not after, and the differences before and after treatment were significant. A similar pattern was noted in the left hemisphere. A brain circuit involving these brain regions may mediate obsessive-compulsive disorder symptoms.

Disruption of social circadian rhythms in major depression: a preliminary report.

While dysregulations of physiological circadian rhythms are common findings in depression and have been posited to be involved in the mediation of depressive episodes, only recently has the role of social circadian rhythms in the pathogenesis of depression been a focus of interest. The Social Rhythm Metric (SRM), designed to describe the regularity of a human subject's social circadian rhythms, was used in this study to compare the social rhythms of depressed patients with those of normal controls and to determine the relationship between SRM scores and depression severity. Depressed patients' SRM scores were significantly lower than those of normal controls. The SRM negatively correlated with scores on the Hamilton Rating Scale for Depression. Overall social activity was negatively correlated with a Hamilton item, social activity impairment. The results of this preliminary study support the hypothesis that social zeitgebers are disrupted in major depression.

Psychiatric, genetic, and positron emission tomographic evaluation of persons at risk for Huntington's disease.

We examined chorea-free subjects at risk for Huntington's disease (n = 52) for lifetime psychiatric diagnoses, present mood, genetic marker status, and caudate glucose metabolic rates with positron emission tomography. Based on previous work, a caudate-ipsilateral hemisphere ratio less than 1.15 was defined as abnormal and predictive of Huntington's disease. None of three methods used to segregate subjects into groups more and less likely to develop Huntington's disease gave significant group rate differences for any formal psychiatric diagnoses. On present mood testing, however, subjective "anger/hostility" was significantly higher in those likely, compared with those less likely, to develop Huntington's disease, as determined by all three methods.

Positron emission tomography and familial Alzheimer's disease: a pilot study.

OBJECTIVE: Local cerebral metabolic rates for glucose were compared between patients with familial Alzheimer's disease (FAD), sporadic Alzheimer's Disease (SAD), and normal controls (NC) to determine if FAD is associated with a unique pattern of brain metabolism. DESIGN: Case-control study matched to convenience sample of FAD. METHODS: Subjects in the three diagnostic groups were scanned using fluorodeoxyglucose and the Positron Emission Tomographic (PET) technique. The criterion standard of a detailed clinical history and examination were compared to scan results. SETTING: Patients in a university hospital. SUBJECTS: Ambulatory controls and Alzheimer's patients, both sporadic (n = 8) and familial (n = 7). The two groups were similar in severity of cognitive dysfunction. RESULTS: FAD and SAD patients did not significantly differ in terms of local cerebral metabolic rates for glucose.

Changes in glucose metabolism in dementia of the Alzheimer type compared with depression: a preliminary report.

We evaluated positron emission tomography (PET) in the differential diagnosis of depression and Alzheimer's disease. The local cerebral metabolic rate for glucose (LCMRGlc) in the parahippocampal gyrus-hippocampus and the dorsolateral prefrontal cortex were determined. The ratio of the LCMRGlc in those two regions was examined in patients with unipolar depression, bipolar depression, and Alzheimer's dementia. An analysis of variance revealed significant overall intergroup differences in values for both hemispheres. Student's t test showed significant differences in LCMRGlc for both unipolar and bipolar depression as compared with Alzheimer's dementia. These data indicate that PET may be useful in the differential diagnosis of dementia vs. depression.

Effects of partial sleep deprivation on the diurnal variation of mood and motor activity in major depression.

Partial sleep deprivation (PSD), keeping a subject awake from 2 AM to 9 PM produces an acute mood improvement in 60% of patients with major depression. We sought to characterize the timing, subcomponent mood, and motor activity changes of this response. Thirty-seven subjects with major depression were rated with the 6-item Hamilton Depression Scale (HAM-6) at 1 PM and completed the Profile of Mood States (POMS) every 2 hr on the day before and day of PSD. Locomotor activity was monitored continuously during the trial with an automated device. Bipolar I patients responded more frequently than other groups. Positive mood responders had greater improvement than nonresponders in POMS subscales of depression, tension, confusion, and anger. The mood improvement increased steadily during the day, peaked in late afternoon, and declined thereafter. Responders showed significantly higher levels of locomotor activity on the baseline pre-PSD day than did nonresponders. All subjects increased motor activity following sleep deprivation, however.