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Biomedical subjects

Jack M Gorman

Publications and source records attributed to Jack M Gorman.

At least 19 recordsLinked to original sources
PubMed2006

Rater bias in a blinded randomized placebo-controlled psychiatry trial.

Rater bias occurs when rater knowledge of treatment assignment modifies the outcome assessment. Raters may be unconsciously influenced by inclinations for or against a particular treatment and consequently may give a more or less generous assessment depending upon these biases. Blinding of raters by keeping raters unaware of treatment assignment is one way to limit bias influencing assessment due to knowledge of treatment assignment. Unblinding may be particularly problematic in efficacy studies comparing placebo to drugs and/or non-drug psychotherapy treatments where subjects may reveal drug side-effects or mention their therapist by name, thus unblinding their treatment assignment. We present a new instrumental variable statistical approach for assessing the association between success in blinding and its impact on efficacy estimates of active drug and/or cognitive behavioural psychotherapy versus placebo in the multicentre comparative treatment study of panic disorder. Despite the uncertainty involved in assessing bias that may be unobserved and unconscious, we will show how to derive a bound for the impact of rater bias.

Bias↗
PubMed2006

Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: relationship to IQ and early trauma.

We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H-MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in comparison to healthy volunteers. A recent study indicates that the volume of prefrontal cortical white matter may be disproportionately increased in man in comparison to other primate species, with evolutionary implications. We therefore re-analyzed the identical scans with a specific focus on the centrum semiovale (CSO) as a representative region of interest of cerebral white matter. The central hypothesis was, in accordance with our gray matter findings, that patients with GAD, in comparison to healthy controls, would exhibit either an increase in NAA in CSO, or alternatively demonstrate reductions in concentrations of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR). MRSI scans that were obtained from an earlier [Mathew, S.J., Mao, X., Coplan, J.D., Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. American Journal of Psychiatry 161, 1119-1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy age- and sex-matched volunteers were analyzed further for CSO metabolite alterations. Self-reported worry was scored using the Penn State Worry Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serial multislice/multivoxel MRSI scans had been performed on a 1.5-T MRI. Using absolute quantification methods for metabolite concentrations, we examined NAA, CHO and CR. GAD patients without ET exhibited bilaterally decreased concentrations of CHO and CR in CSO in comparison to healthy volunteers, whereas GAD patients with ET were indistinguishable from controls. In patients with GAD, high IQ was paired with greater worry, whereas in healthy volunteers, high IQ was associated with less worry. In all subjects, IQ inversely predicted left and right CSO CHO concentrations, independent of age, sex, group assignment and PSWQ scores. The CSO may therefore represent a neural substrate that exhibits reductions in CHO and CR metabolite concentrations that are inversely associated with GAD symptomatology and, in the case of CHO, with intelligence. These conclusions are deemed preliminary due to small sample size, with further study of cerebral WM in anxiety disorders suggested.

Adult↗
PubMed2006

Low cerebrospinal fluid transthyretin levels in depression: correlations with suicidal ideation and low serotonin function.

BACKGROUND: Transthyretin (TTR) is a thyroid hormone binding protein synthesized by choroid plexus and secreted into cerebrospinal fluid (CSF). We sought to replicate and extend our previous findings of lower CSF TTR in depression. METHODS: Cerebrospinal fluid TTR concentrations of 17 medication-free patients with major depressive disorder (MDD) and 15 healthy individuals were determined by a sensitive, specific radioimmunoassay newly developed in our laboratory (ESL, TBC). RESULTS: Cerebrospinal fluid TTR was lower in the MDD patients compared with healthy volunteers (mean +/- SD, 19.7 +/- 1.6 vs. 21.8 +/- 2.2 mg/L, p = .005). Age correlated positively with CSF TTR (r = .38, p < .05). The group difference remained significant (p < .005) after covariance for age. Within the MDD group, Scale for Suicide Ideation total score correlated inversely with CSF TTR (beta = -.58, p < .05). In the entire sample of depressed and healthy individuals, CSF 5-hydroxyindoleacetic acid (5-HIAA) correlated positively (beta = .34, p < .05) with CSF TTR. CONCLUSIONS: We replicated our finding of low CSF TTR levels in depression and newly identified two relationships that may explain reports linking thyroid axis dysfunction and suicidal behaviors. Serotonergic hypofunction in depression, reflected by low CSF 5-HIAA, may result in decreased choroid plexus TTR production, alterations in central thyroid hormone kinetics, and increased vulnerability to suicidal ideation and perhaps suicide.

Adult↗
PubMed2006

Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression.

CONTEXT: The hallmark pathological changes in Alzheimer disease (AD) are abundant plaque and tangle formation, especially in the temporal lobes and hippocampus. Although there is increasing evidence that major depression may interact with neuropathological processes in AD, there have been no studies of neuropathological changes in AD as a function of history of major depression. OBJECTIVE: To test the hypothesis that neuritic plaques and neurofibrillary tangles are more pronounced in the hippocampus of patients with AD with a lifetime history of major depressive disorder, as compared with patients with AD without depression history. DESIGN: Postmortem study. SETTING: Nursing home. PARTICIPANTS: The brains of 52 patients with AD without a lifetime history of major depression were compared with the brains of 50 patients with AD with a lifetime history of major depression. MAIN OUTCOME MEASURES: Neuropathological ratings from the Consortium to Establish a Registry in Alzheimer Disease battery. RESULTS: Brains of patients with AD with a lifetime history of depression showed higher levels of both plaque (P<.005) and tangle (P<.002) formation within the hippocampus than brains of patients with AD without a history of depression. Post hoc analyses showed that patients with AD who had a history of depression exhibited more rapid cognitive decline than patients without a history of depression (P<.004). Furthermore, within the group of patients with AD with a history of depression, patients who exhibited concurrent depression at the time of first diagnosis of AD exhibited more pronounced neuropathological changes in the hippocampus (P<.006). CONCLUSIONS: In AD, the presence of a lifetime history of depression corresponds to increases in AD-related neuropathological changes within the hippocampus. These changes go along with more rapid cognitive decline in patients with AD with a history of depression, and are more pronounced in patients with AD suffering from depression early on in the disease process, suggesting an interaction between major depression and AD neuropathology.

Age Factors↗
PubMed2006

Psychiatric behavioral aspects of comanagement of hepatitis C virus and HIV.

Coinfection with HIV hastens the progression of liver disease in persons with hepatitis C virus (HCV) infection. As mortality directly due to HIV continues to decrease among persons who are HIV-positive, coinfection with HCV has emerged as a leading cause of death. There is increasing attention to the need to actively treat HCV infection in HIV/HCV coinfected patients. Current HCV treatment with pegylated interferon and ribavirin achieves sustained viral response in up to 40% of coinfected patients but has numerous neuropsychiatric side effects. Providers are hesitant to begin HCV treatment in the coinfected population given the high prevalence of existing psychiatric illness, cognitive impairment, and substance use disorders. There is an urgent need for research into the psychiatric and behavioral predictors of HCV treatment adherence and virologic outcome, as well as into the optimal psychiatric management of the neuropsychiatric sequelae of HCV therapy.

Antidepressive Agents↗
PubMed2006

Advances in the treatment of anxiety: targeting glutamate.

Our current psychopharmacological treatments for anxiety disorders evince a number of shortcomings, including troublesome side effects and lack of primary effects. Whereas many new drugs have been developed in the past few decades, most are based on outmoded theories of the pathogenesis of these disorders (i.e., monoamine hypotheses), thus frustrating our ability to create more specific and effective interventions. Recently, however, the neurobiological literature has shown a convergence of findings focusing on the glutamatergic system in anxiety disorders, and the growth of pharmacological tools targeting these receptors has led to the development of novel treatments having anxiolytic effects in humans and animals alike. Additionally, as this system is showing promise as a final common pathway in the pathogenesis of anxiety disorders, we may be able to employ glutamate-specific neuroimaging techniques (e.g., N-acetyl-aspartate, GLX) to both guide treatment decisions and present reliable objective biomarkers for treatment efficacy.

Antidepressive Agents↗
PubMed2006

Gender differences in depression and response to psychotropic medication.

BACKGROUND: In the United States, depression is approximately twice as common among women as among men, across all age groups. OBJECTIVE: This review examines gender differences in the epidemiology and clinical presentation of depression, and explores whether women respond differently than men to antidepressant medications. METHODS: This is a selective review focusing on current issues in the management of depression, with particular attention to gender differences in the epidemiology, diagnosis, and treatment of the disease. RESULTS: Women are more likely than men to have atypical symptoms of depression (eg, hypersomnia, hyperphagia), to have comorbid anxiety disorders, and to attempt suicide. Women are also more likely to have seasonal affective disorder. Mood and anxiety symptoms that seem to be related to the menstrual cycle do not often represent genuine premenstrual dysphoria, but when premenstrual dysphoric disorder does occur, its impact on quality of life is similar to that of major depressive disorder. There is ongoing controversy about whether men and women respond equally well to antidepressant medications, and preliminary evidence suggests that selective serotonin reuptake inhibitors (SSRIs) are more effective in the presence of estrogen. Depression affects about 10% of pregnant women. Antidepressant medication should be considered during pregnancy if depression is moderate or severe, or if withdrawal of maintenance medication is likely to result in recurrent depression. The potential benefits of using antidepressant medications in a pregnant or breastfeeding woman should be balanced against the potential risks to the newborn. Because of the risk of neonatal withdrawal syndrome, SSRIs should be used at the lowest effective dose during the third trimester of pregnancy and should be tapered before delivery. CONCLUSIONS: Continuing research is needed to determine how gender influences the risk, clinical presentation, and response to treatment of depression. Exploration of sex differences in animals and humans should aid in efforts to treat depression as an organic disorder rather than a psychological maladaptation.

Antipsychotic Agents↗