Thyroid stimulation test in healthy subjects and psychiatric patients

Fifteen healthy women and 64 female psychiatric inpatients (major depression: 17, schizophrenia: 24, alcohol dependence: 9, and adjustment disorder: 14 cases) without identifiable thyroid dysfunction were investigated with the TRH test under comparable circumstances. Although all patient groups showed some tendency toward lower baseline TSH and smaller TRH-induced TSH responses, only patients with major depression demonstrated marked, statistically significant differences from controls in both variables. Women with alcohol dependence (in the early withdrawal period) showed significantly decreased TSH responses to TRH but only a weak tendency to lower basal TSH levels. Intergroup differences in the TSH response remained significant after correction for basal TSH by analysis of covariance. Neither variables correlated significantly with age, weight or body height, but baseline TSH correlated with body surface. The TRH test, using only 0.2 mg TRH for stimulation, seemed to be useful for identifying major depression and showed that early withdrawal from alcohol may be a factor to be considered in similar studies.     

The metyrapone test in manic patients and healthy subjects

The metyrapone (Metopiron) test (MT), a useful and reliable procedure for assessing hypothalamic-pituitary-adrenal (HPA) axis function, was applied to manic patients and healthy subjects. Three out of 11 patients had high normal responses to metyrapone, as observed in patients with Cushing's disease. One patient exhibited a subnormal response to metyrapone, as occurs in patients with adrenal insufficiency. No such abnormalities were detected in 11 matched healthy control subjects. These preliminary results suggest that the HPA axis activity patterns in mania may be more complex than previously reported.     

The metyrapone test in schizophrenic patients and healthy subjects

The metyrapone test, a useful and reliable procedure for assessing hypothalamic-pituitary-adrenocortical (HPA) axis function, was applied to schizophrenic patients and healthy controls. 4 out of 18 patients had subnormal responses to metyrapone whereas there were no such cases in the 22 control subjects. 1 schizophrenic patient and 3 control subjects had high normal responses to metyrapone. The relationship with the dexamethasone suppression test was found to be complex. These preliminary results suggest that the HPA axis activity patterns in psychiatric illness may be more complicated than previously reported.     

A pilot study of a neuroendocrine test battery in posttraumatic stress disorder

Eight female patients who fulfilled DSM-III criteria for posttraumatic stress disorder (PTSD) took part in this study. They were each assessed using the dexamethasone suppression test, the desipramine/growth hormone stimulation test, which examines alpha-2-adrenoceptor functioning, and the buspirone/prolactin test, which is thought to examine 5-HT receptor functioning. A control group consisting of age- and sex-matched healthy subjects was also tested. For each subject the three tests were conducted over 5 days. Hormone assays were carried out blind to diagnosis. Overall no differences on any of the three tests were detected between the patients and controls. The results do not support a link between PTSD and major depression.     

DTI tractography and white matter fiber tract characteristics in euthymic bipolar I patients and healthy control subjects

With the introduction of diffusion tensor imaging (DTI), structural differences in white matter (WM) architecture between psychiatric populations and healthy controls can be systematically observed and measured. In particular, DTI-tractography can be used to assess WM characteristics over the entire extent of WM tracts and aggregated fiber bundles. Using 64-direction DTI scanning in 27 participants with bipolar disorder (BD) and 26 age-and-gender-matched healthy control subjects, we compared relative length, density, and fractional anisotrophy (FA) of WM tracts involved in emotion regulation or theorized to be important neural components in BD neuropathology. We interactively isolated 22 known white matter tracts using region-of-interest placement (TrackVis software program) and then computed relative tract length, density, and integrity. BD subjects demonstrated significantly shorter WM tracts in the genu, body and splenium of the corpus callosum compared to healthy controls. Additionally, bipolar subjects exhibited reduced fiber density in the genu and body of the corpus callosum, and in the inferior longitudinal fasciculus bilaterally. In the left uncinate fasciculus, however, BD subjects exhibited significantly greater fiber density than healthy controls. There were no significant differences between groups in WM tract FA for those tracts that began and ended in the brain. The significance of differences in tract length and fiber density in BD is discussed.     

The interlocking finger test in patients with Parkinson’s disease and healthy subjects

The interlocking finger test (ILFT) is a bedside screening test in which the subject must imitate four bimanual finger gestures without symbolic meaning. We assessed the utility of the test in the cognitive evaluation of patients with Parkinson’s disease (PD). We evaluated 88 healthy subjects and 101 patients with PD using a simplified motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr and Schwab and England scales, Geriatric Depression Scale, Pfeffer Functional Activities Questionnaire, Clinical Dementia Rating, Mini-Mental State Examination, clock drawing test, digit span, word list battery of the Consortium to Establish a Registry for Alzheimer’s Disease assessment, Frontal Assessment Battery, semantic verbal fluency test, and the ILFT. Diagnoses of mild cognitive impairment and dementia were made using the Movement Disorder Society diagnostic criteria. ILFT scores in healthy subjects correlated significantly with age (p = 0.001) and only one healthy subject scored 2 in the test. ILFT scores were significantly lower in patients with PD and dementia (p = 0.001) and significantly correlated with cognitive and functional tests, but not with depressive symptoms (p = 0.607), Hoehn and Yahr scores (p = 0.907), or Schwab and England scores (p = 0.701). Twenty-five patients with dementia, three patients with mild cognitive impairment, and six patients with apparently normal cognition scored less than 3 in the ILFT. The area under the receiver operating characteristic curve for the ILFT to discriminate patients with dementia from those without it was 0.76 (cut-off score of 3/2: sensitivity of 61%, specificity of 0.85). In conclusion, the ILFT seems to be a useful bedside test to assess cognitive impairment in patients with PD.     

Serotonin function and depression: neuroendocrine and mood responses to intravenous L-tryptophan in depressed patients and healthy comparison subjects

OBJECTIVE: This study was designed to compare central serotonergic function in depressed patients and healthy comparison subjects by examining neuroendocrine and mood responses to intravenous L-tryptophan. METHOD: One hundred twenty-six drug-free patients with DSM-III-R major depression (109 unipolar, 17 bipolar; 68 melancholic, 58 nonmelancholic; 28 psychotic, and 98 nonpsychotic patients) and 58 healthy comparison subjects participated. After an overnight fast, subjects received an intravenous infusion of L-tryptophan, 7 g. Blood was obtained for determination of serum prolactin, serum growth hormone (GH), and plasma tryptophan levels. Visual analogue scales were used to assess mood. RESULTS: Prolactin responses were blunted in nonmelancholic and higher in melancholic and psychotic depressed patients, while GH responses were blunted in combined unipolar, nonmelancholic, and nonpsychotic depressed patients. Controlling for baseline biological, clinical, and demographic factors eliminated the higher prolactin response in the melancholic and psychotic patients, attenuated the blunted GH response in the unipolar patients, and revealed a blunted GH response in the melancholic patients. Patients and comparison subjects differed on five of 13 mood responses, primarily because of baseline differences. CONCLUSIONS: These findings are consistent with previous studies demonstrating blunted neuroendocrine responses to intravenous L-tryptophan in depression. Restriction of these findings to specific subtypes of depression may reflect a differential role of serotonergic abnormalities in these subtypes.     

Weight loss causes neuroendocrine disturbances: experimental study in healthy starving subjects

A variety of endocrine dysfunctions have been reported for anorexia nervosa, protein caloric malnutrition, and depression. The effect of reduced caloric intake and weight loss on endocrine functions was assessed in an experiment with five healthy female subjects during an initial baseline phase, a 3-week phase of complete food abstinence, weight gain to the original level, and a final baseline phase. During fasting, disturbances in hypothalamic-pituitary-adrenal function were observed, with elevated plasma cortisol levels, increase in the number of secretory episodes, increase in cortisol plasma half-life, and insufficient suppression following 1.5 mg dexamethasone. While all dexamethasone suppression tests (DSTs) were normal at baseline, 7 of 14 DSTs showed insufficient suppression in the fasting phase. During fasting, basal thyroid-stimulating hormone (TSH) values were lowered and the TSH response to thyrotropin-releasing hormone (TRH) was blunted. The plasma level of growth hormone (GH) over 24 hours was elevated during fasting and administration of the alpha 2-adrenergic receptor agonist clonidine resulted in a subnormal GH response after restoration of original body weight. One of the five subjects showed increased irritability, distress, anxiety, and depression as measured by various psychological scales. The results show that reduced caloric intake, weight loss, or catabolic state have powerful effects on several endocrine systems. The specificity of measures of endocrine disturbances (DST, TRH tests, and clonidine tests) as biological markers for certain types of depression must be questioned, and the metabolic state should be given more consideration in future studies.     

Uncoupler-accelerated efflux of 5-hydroxytryptamine from platelets of healthy subjects and patients with unipolar and bipolar depression

The efflux of 14C-5-hydroxytryptamine (5HT) from platelets of 25 depressed patients (16 unipolar and 9 bipolar) and 22 control subjects was studied in the presence of carbamyl cyanide m-chlorophenylhydrazone (FCCP), which dissipates H+ gradients. FCCP (0.31 microM), at 10 minutes' incubation time, enhanced the efflux of 14C-5HT to a significantly higher extent from platelets of patients with bipolar depression than from platelets of control subjects. An analysis of variance revealed a significant interaction between the diagnostic categories (unipolar, bipolar, and control) and sex in accounting for variation of the FCCP-evoked efflux. The diagnostic category X sex effect was also significant. The results reported indicate that the FCCP-evoked efflux of 5HT is an easily measured biochemical parameter of possible diagnostic interest.     

Psychological, autonomic and neuroendocrine responses to acute stressors in the combined dexamethasone/CRH test: a study in healthy subjects

The combined dexamethasone/CRH test (DEX/CRH test) is reported to produce augmented ACTH and cortisol responses in various psychiatric disorders as well as in some non-psychiatric conditions. To examine whether stress affects the outcome of DEX/CRH test, two stress groups in a repeated measures design were compared to an age-matched control group with regard to the psychological, autonomic and neuroendocrine responses after the combined dexamethasone and CRH challenge. Cold pressor (4 degrees C, total 10 min) produced stronger subjective distress than mental arithmetic (15 min). Cold exposure, but not the mental test, elevated systolic and diastolic blood pressure, whereas the mental test increased pulse rate and skin conductance level more markedly than cold exposure. Neither stressor produced a significantly enhanced response of ACTH and cortisol in DEX/CRH test, and there was no correlation between psychological and neuroendocrine responses. These findings suggest that different stressors induce different patterns of sympathetic activation and that acute stress is unlikely to affect the results of DEX/CRH test.     

Visceral pain and public speaking stress: neuroendocrine and immune cell responses in healthy subjects

Whereas responses to psychological stressors are well-characterized, little is known regarding responses to painful visceral stimuli. We analyzed the emotional, cardiovascular, neuroendocrine, and cellular immune responses to painful rectal stimulation and psychological stress in healthy individuals. Eleven healthy subjects were studied in three conditions on separate days: painful rectal distension, public speaking stress, and rest. Blood was drawn for endocrinological and immunological analyses; heart rate and blood pressure were measured continuously; state anxiety was assessed with a questionnaire (STAI-S). Anxiety scores were highest in the rectal distension condition. This was evident following rectal distension (mean STAI-S scores: 44.2+/-3.5 post-distension vs. 36.6+/-3.8 post-speech, p<.05), but anxiety was also elevated at baseline (41.6+/-3.9 vs. 32+/-3.2 recovery, p<.01). This anticipatory effect was reflected by elevated baseline cortisol (p<.05) and baseline ACTH (p<.01) levels, as well as circulating lymphocytes and lymphocyte subsets, including decreased basal CD3+CD4+ cells (p<.05) and increased CD16+CD56+ cells (p=.06) compared to rest. Both public speech and rectal distension induced cardiovascular activation, but the effect was more pronounced following rectal distension (+63.8+/-9.4 mmHg in response to distension vs. +36.4+/-6.2 mmHg in response to speech for systolic BP, p<.05). Different response patterns were also observed in the distribution of circulating leukocytes and lymphocyte subsets, including CD16+CD56+ cells (p<.05). An acute visceral pain stimulus causes profound emotional, neuroendocrine, and immune cell responses, which are markedly affected by anticipatory anxiety. These findings may have implications for conditions associated with visceral hyperalgesia.     

Cognitive impairment in schizoaffective disorder: a comparison with non-psychotic bipolar and healthy subjects

Objective: Only a few studies have examined specifically the neuropsychological performance of schizoaffective patients. Method: The sample consisted of 34 euthymic DSM‐IV schizoaffective patients, who were compared with 41 euthymic bipolar patients without history of psychotic symptoms and 35 healthy controls. Euthymia was defined by a score of 6 or less at the Young Mania Rating Scale and a score of 8 or less at the Hamilton Depression Rating Scale for at least 6 months. Patients were compared with several clinical, occupational, and neuropsychological variables such as executive function, attention, verbal and visual memory and the two groups were contrasted with 35 healthy controls on cognitive performance. The three groups were compared using mancova after checking the potential role of several co‐variables. Results: Schizoaffective patients showed greater impairment than controls and bipolar patients, in several domains, including verbal memory, executive function, and attentional measures. Bipolar patients without history of psychosis performed similar to the controls except for verbal fluency. Conclusion: Schizoaffective disorder carries more neurocognitive impairment than non‐psychotic bipolar disorder and more occupational difficulties.     

Emotional modulation of response inhibition in stable patients with bipolar I disorder: a comparison with healthy and schizophrenia subjects

Gopin CB, Burdick KE, DeRosse P, Goldberg TE, Malhotra AK. Emotional modulation of response inhibition in stable patients with bipolar I disorder: a comparison with healthy and schizophrenia subjects.
Bipolar Disord 2011: 13: 164–172. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Bipolar disorder (BD) has been associated with impairment in affective processing during depressive and manic states; however, there are limited data as to whether this population exhibits such difficulty during stable periods. We examined the pattern of affective processing in stable BD patients and compared their profile to that of healthy controls (HC) and patients diagnosed with schizophrenia (SZ). Methods: A total of 336 subjects were administered an Affective Go/No‐go test to evaluate target detection of negatively valenced, positively valenced, and neutral stimuli. Accuracy and response bias served as dependent variables in a series of multivariate analyses of covariance to test for group differences. Results: The BD group relative to the HC group exhibited response biases toward negatively valenced information (p < 0.01). Deficits were also evident in discrimination of and accurate responses to positively valenced information in the BD group versus the HC group (p < 0.05). In contrast to the controls, the SZ group performed poorly on all task components and was less accurate across all conditions regardless of affective valence (p < 0.01). Patients with SZ evidenced reverse biases for positive information, as they were less likely to respond to positive words (p < 0.05) despite comparable response bias on neutral and negative conditions. Conclusions: Affective processing impairment evident in BD is a feature of the disorder that is present even during stable periods. Prior studies comparing BD with SZ have highlighted clear quantitative but inconsistent qualitative differences in cognitive functioning. Our data suggest that a response bias toward negative stimuli may be a critical and relatively specific feature of BD.     

A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects

Périco CA‐M, Duran FLS, Zanetti MV, Santos LC, Murray RM, Scazufca M, Menezes PR, Busatto GF, Schaufelberger MS. A population‐based morphometric MRI study in patients with first‐episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects.
Bipolar Disord 2011: 13: 28–40. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Many morphometric magnetic resonance imaging (MRI) studies that have investigated the presence of gray matter (GM) volume abnormalities associated with the diagnosis of bipolar disorder (BD) have reported conflicting findings. None of these studies has compared patients with recent‐onset psychotic BD with asymptomatic controls selected from exactly the same environment using epidemiological methods, or has directly contrasted BD patients against subjects with first‐onset psychotic major depressive disorder (MDD). We examined structural brain differences between (i) BD (type I) subjects and MDD subjects with psychotic features in their first contact with the healthcare system in Brazil, and (ii) these two mood disorder groups relative to a sample of geographically matched asymptomatic controls. Methods: A total of 26 BD subjects, 20 subjects with MDD, and 94 healthy controls were examined using either of two identical MRI scanners and acquisition protocols. Diagnoses were based on DSM‐IV criteria and confirmed one year after brain scanning. Image processing was conducted using voxel‐based morphometry. Results: The BD group showed increased volume of the right dorsal anterior cingulate cortex relative to controls, while the MDD subjects exhibited bilateral foci GM deficits in the dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons). Direct comparison between BD and MDD patients showed a focus of GM reduction in the right‐sided dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons) and a trend (p < 0.10, corrected) toward left‐sided GM deficits in the dorsolateral prefrontal cortex of MDD patients. When analyses were repeated with scanner site as a confounding covariate the finding of increased right anterior cingulate volumes in BD patients relative to controls remained statistically significant (p = 0.01, corrected for multiple comparisons). Conclusions: These findings reinforce the view that there are important pathophysiological distinctions between BD and MDD, and indicate that subtle dorsal anterior cingulate abnormalities may be relevant to the pathophysiology of BD.     

High trait anxiety in healthy subjects is associated with low neuroendocrine activity during psychosocial stress

Altered stress responsiveness has been repeatedly related to mood and anxiety disorders. In a traditional view, a reduction of the stress response has been thought favorable. The goal of the present study was to verify the hypothesis that high anxiety is accompanied by enhanced hormone release during stress. Healthy subjects at the upper (anxious, n=15) and lower (non-anxious, n=12) limits of the normal range of a trait anxiety scale (State trait anxiety inventory) were exposed to psychosocial stress procedure based on public speech. Hormone levels, cardiovascular activation and skin conductance were measured. Exposure to psychosocial stress was associated with significant increases of all parameters measured. During the stress procedure, subjects with high trait anxiety exhibited lower levels of hormones of the hypothalamo–pituitary–adrenocortical axis, namely ACTH and cortisol in plasma, as well as cortisol in saliva. Similarly, the stress-induced activation of epinephrine, norepinephrine and prolactin secretion was significantly lower in anxious subjects in comparison with that in non-anxious subjects. Thus, in contrast to the traditional view, high anxiousness was not associated with exaggerated stress response. Our findings suggest that high trait anxiety may be associated with an inability to respond with adequate hormone release to acute stress stimuli.     

A miRNome analysis of drug-free manic psychotic bipolar patients versus healthy controls

European Archives of Psychiatry and Clinical Neuroscience - The lifetime presence of psychotic symptoms is associated with more clinical severity, poorer outcome and biological changes in patients...