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Repetitive transcranial magnetic stimulation (rTMS) is a tool with antidepressant potential that uses a coil placed on the scalp to produce a powerful magnetic field that directly stimulates only the outermost cortex. MRI scans were obtained in 29 depressed adults involved in an rTMS antidepressant clinical treatment. These scans were analyzed to investigate the effect of distance from coil to cortex on clinical parameters. Longer motor cortex distance, but not prefrontal distance, strongly correlated with increased motor threshold (P

Lateral ventricle enlargement in schizophrenia has been positively correlated with poor premorbid competence, negative symptoms, and poor treatment response and negatively correlated with concentrations of homovanillic acid (HVA), a dopaminergic metabolite. The authors provide further evidence of a reciprocal relationship between lateral ventricle size and dopaminergic activity in schizophrenia.They assessed the relationship between lateral ventricle enlargement (ventricle-brain ratio, VBR) and CSF neurotransmitter metabolite concentrations (HVA and 5-hydroxyindoleacetic acid [5-HIAA]) in 45 patients with schizophrenia, 28 with affective disorders (19 patients with major depression and nine with bipolar disorder), and 91 normal comparison subjects.No group mean differences were significant. Although individual correlations of VBR with HVA and 5-HIAA were not statistically significant, the ratio of HVA to 5-HIAA was significantly correlated with VBR in the patients with schizophrenia, a finding consistent with dopaminergic-serotonergic balance hypotheses.These data suggest that it is the balance between HVA and 5-HIAA rather than their absolute levels which is associated with brain morphology and that this relationship between brain chemistry and morphology may be characteristic of the normal range of functioning for these systems. In other words, independent of whether brain morphology and chemistry differentiate psychopathological from nonpsychopathological states, there may be an orderly relationship between lateral ventricle size and the balance between HVA and 5-HIAA balance that is especially prominent in schizophrenia.

The study of sexual dimorphism in brain morphology may help delineate subtypes of schizophrenia based, in part, on sex; yield insight into the relationship between brain structure and behavior; and provide a neurodevelopmental context for studying the ontogenesis of schizophrenia. Preliminary findings from an ongoing study of sex differences in brain morphology and neuropsychological performance in schizophrenia suggest that schizophrenic males are characterized by multiple morphological deviations; this may represent an extreme form of normal sexual dimorphism in brain morphology. The role of brain morphology deviation in the ontogenesis of schizophrenia is discussed.

Background: The proper treatment of mood disorders occurring during pregnancy is a major therapeutic problem since no antidepressant medications have been established as safe for the developing fetus. Several double-blind placebo-controlled studies have explored the efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression. Case: We report the case of a 36-year-old woman in her second trimester of pregnancy, whose depression (DSM-IV) and anxiety were successfully treated with rTMS. Further studies of rTMS in depressed pregnant women appear warranted.

Relative regional brain blood flow was measured in 23 clinically depressed adults by using ECD SPECT at baseline and again during actual prefrontal transcranial magnetic stimulation (TMS) following 5 daily sessions of TMS. TMS over prefrontal cortex caused increased activity in cortex directly under the stimulation (inversely correlated with distance from scalp to cortex) and decreased activity in remote regions (anterior cingulate and anterior temporal poles). High-frequency rTMS (20 Hz) caused more relative flow immediately below the TMS coil than did low-frequency rTMS (5 Hz). Confirming the hypotheses tested, repeated daily TMS over the prefrontal cortex in medication-free depressed adults appears to change both local and remote blood flow in a manner that may also depend on the frequency of stimulation and coil to outer cortex distance.

The effects of the herb St. John's wort (Hypericum perforatum), a purported antidepressant, on the activity of cytochrome P-450 (CYP) 2D6 and 3A4 was assessed in seven normal volunteers. Probe substrates dextromethorphan (2D6 activity) and alprazolam (3A4 activity) were administered orally with and without the co-administration of St. John's wort. Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic ratios (DMRs) determined. Plasma samples were collected (0-60 hrs) for alprazolam pharmacokinetic analysis sufficient to estimate tmax, Cmax, t 1/2, and AUC. Validated HPLC methods were used to quantify all compounds of interest. No statistically significant differences were found in any estimated pharmacokinetic parameter for alprazolam or DMRs. These results suggest that St. John's wort, when taken at recommended doses for depression, is unlikely to inhibit CYP 2D6 or CYP 3A4 activity.

Extrapyramidal symptoms (EPS) including parkinsonism, akathisia, dystonia, and tardive dyskinesia have commonly been associated with acute or chronic administration of neuroleptic drugs. A review of the medical literature reveals a substantial number of cases with similar clinical characteristics associated with the tricyclic antidepressants, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). Although the data are not sufficient to make definitive pharmacoepidemiologic conclusions, the available number of case reports suggests the SSRIs may be more common offenders in producing these adverse drug effects. The exact mechanism is elusive but likely involves complex interactions of dopamine, serotonin, and norepinephrine between cortical structures and the basal ganglia. The final common pathway for production of EPS seems to be indirect modulation of dopaminergic function. Predictors of patients at risk for antidepressant-induced EPS are not established, but a greater awareness of the potential for these drug side effects to occur may increase their recognition and decrease antidepressant-induced morbidity.

Natural killer cell activity was prospectively studied in 15 patients with chronic schizophrenia and in seven patients with schizoaffective disorder, depressed type. These patients were compared to individually matched normal controls. No mean differences in natural killer cell activity between the patient groups and their controls were observed.

Objective As part of an ongoing study investigating the relationship between brain morphology/function and neuropsychological performance in psychopathology, the authors conducted brain magnetic resonance imaging (MRI) studies to investigate the prevalence and psychiatric significance of white matter hyperintensity signals. Method Brain MRI acquisition was done with 0.5 and 1.5 Tesla Philips scanners. Psychiatric subjects (N = 229) and normal volunteers (N = 154) were recruited by newspaper and local advertising and by physician referral. DSM-III-R criteria were used. White matter hyperintensity signals were rated on a 4-point scale of severity. Prevalence rates and risk ratios were calculated. Results Prevalence rates of hyperintensity signals in all psychiatric subjects (mean age = 34 years, SD = 9) and normal volunteers (mean age = 34, SD = 10) were 6.6% and 9.1%, respectively (a nonsignificant difference). When all psychiatric subjects, subjects under age 45, and subjects age 45 and over in a diagnostic category were considered, there were no statistically significant differences between them and normal volunteers in the same age groups in prevalence of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, and obsessive-compulsive disorder. A significant difference existed between the severity of deep white matter hyperintensity signals in subjects with major depression and normal volunteers. Older age was correlated as a risk factor for white matter hyperintensity signals for psychiatric subjects. Conclusions These results do not support previous findings of greater prevalence of hyperintensity signals in bipolar disorder. Significantly higher prevalence rates of hyperintensity signals were seen in subjects with major depression only when severity of the deep white matter hyperintensity signals was considered. Older age is an indirect risk factor for the presence of white matter hypertensity signals, probably as a result of vascular changes associated with concurrent medical illnesses.

administered lateral orbitofrontal rTMS to 7 subjects with GAD. On separate days, subjects received right or left high frequency, right or left low frequency, or placebo rTMS in a counterbalanced, single blind, randomized order. Serial self-rated visual analogue scales measuring anxiety and mood were performed. We hypothesized that right high frequency rTMS would increase anxiety whereas right low frequency rTMS would decrease anxiety based on: (1) data suggesting that the orbitofrontal cortex is important in anticipatory anxiety; (2) studies of healthy volunteers and depressed patients as well as a single case report in a GAD patient suggesting that high frequency prefrontal rTMS temporarily increases anxiety, and (3) the theory that high and low frequency rTMS may have opposite effects on brain function. Preliminary analysis reveals that placebo stimulation significantly decreased anxiety during the hour after stimulation. Also, relative to placebo stimulation, a trend exists suggesting that all the active stimulation types were anxiogenic. There did not appear to be a significant difference in anxiety ratings between the active stimulation cells. These results do not support our hypothesis. In fact, they suggest that single session lateral orbitofrontal stimulation may be anxiogenic, regardless of hemisphere or frequency. Pain with the active stimulation cells may have confounded our results.

antidepressanteffectsfor TMS,especiallyleft prefrontalrapidTMS.In normalcontrols,TMS has also been reportedto cause moodchanges specific tObrain side h two separatecontrolledstudies(Georgeet al, 1996;Pascual-Leoneet rd, 1996).Paradoxically,the studiesof normals found increasedsadnesswith left prefrontalstimulationand increased happinesswithrightprefrontalstimulation.ECTis effectivein maniaas well as depression(Smallet al, 1991;Skidaret al, 1994;Black et rd, 1987;Smallet al, 1988).Wethereforeplanneda studyofTMSin mania. Sixteenpatientscompleteda 14daydouble-blindcontrolledtrial of right vs leftprefrontalTMSat 20Hz,2 seconddurationper train,20trainsper day for 10treatmentdays.Maniawas evaluatedusingthe ManiaScale, the Brief PsychiatricRatingScale, and the ClinicalGlobalImpression. Significantlymore improvementwas observedin patientstreated with rightprefrontalTMSthan withleft prefrurrtal.The therapeuticeffect of TMS in mania may show literality oppositeto the effect of TMS in depression.

methodsused and the therapeuticeffeetshavevariedwidely.Important and varying parameters have beerr patient populations,coil shape, neuroanatomiclocation, stimulationintensity and frequency,dosing schedulesand total dose. In order to begin addressingwhichof these parametersare importantin the antidepressanteffect, we organizeda paraflel-design, double-blind, placebo-controlledstudyexplicitlyanafyzing the role of frequency.