Inflammatory, cardio-metabolic and diabetic profiling of chronic schizophrenia.

BACKGROUND: There is a growing interest in low-grade inflammatory and metabolic alterations in patients with chronic schizophrenia (SCH). METHODS: Inflammatory (tumor-necrosis factor-α [TNF-α], interferon-γ [IFN-γ], interleukins [IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10], monocyte chemo-attractant protein-1 [MCP-1]) and growth factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF]) were measured in blood serum samples of 105 SCH patients and 148 control subjects (CS). Simultaneously the clinical biomarkers (C-reactive protein [CRP], triglycerides [TG], low-density lipoprotein [LDL-c] and high-density lipoprotein [HDL-c] cholesterol, glycated hemoglobin [HbA1c]) were measured, and body mass index (BMI) was calculated for patients. RESULTS: Several cyto-/chemokines (IFN-γ, MCP-1, IL-2, IL-6, IL-8 and IL-10) were significantly (P<0.0000001) elevated in SCH patients compared to CS. Odds ratios, obtained from logistic regression analyses, were significantly elevated for IL-2, IL-6, IL-10, INF-γ, and decreased for TNF-α in SCH group. Among the patients, higher IL-2, IL-6, INF-γ and lower MCP-1 levels as well as male gender were together significant (P<0.000001) predictors of higher HbA1c levels, and TG/HDL-c parameter was associated with ratios of INF-γ/IL-10 (P=0.004), and INF-γ/IL-4 (P=0.049), HbA1c (P=0.005), INF-γ (P=0.009), as well as LDL-c (P=0.02) levels. CONCLUSIONS: IL-2, IL-6, IL-10 and IFN-γ were the most significant SCH-related markers among the measured cytokines in our patient group. Furthermore, significant associations between pro-/anti-inflammatory imbalance and HbA1c as well as cardio-metabolic risk marker (TG/HDL-c) were observed, indicating higher risks of diabetes and cardiovascular diseases among SCH patients.

Cortical thickness and surface area correlates with cognitive dysfunction among first-episode psychosis patients.

BACKGROUND: In studies using magnetic resonance imaging (MRI), some have reported specific brain structure-function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS). METHOD: Exploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS. RESULTS: Significant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS. CONCLUSIONS: Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure-function relationship in FEP patients compared with CS.

Social support in depression: structural and functional factors, perceived control and help-seeking.

Aims. This study examined the associations of social support, loneliness and locus of control with depression and help-seeking in persons with major depression. Methods. Twelve-month help-seeking for emotional problems was assessed in a cross-sectional 2006 Estonian Health Survey. Non-institutionalized individuals aged 18-84 years (n = 6105) were interviewed. A major depressive episode was assessed using the Mini-International Neuropsychiatric Interview. Factors describing social support, social and emotional loneliness and locus of control were assessed, and their associations with depression were analysed. The associations with reported help-seeking behaviour among people identified as having a major depressive episode (n = 343) were explored. Results. Low frequency of contacts with one's friends and parents, emotional loneliness, external locus of control and emotional dissatisfaction with couple relations were significant factors predicting depression in the multivariate model. External locus of control was associated with help-seeking in the depressed sample. Interactions of emotional loneliness, locus of control and frequency of contacts with parents significantly predicted help-seeking in the depressed sample. Conclusions. Depression is associated with structural and functional factors of social support and locus of control. Help-seeking of depressed persons depends on locus of control, interactions of emotional loneliness, locus of control and contacts with the parental family.

Associations between LSAMP gene polymorphisms and major depressive disorder and panic disorder.

The purpose of this case-control genetic association study was to explore potential relationships between polymorphisms in the limbic system-associated membrane protein (LSAMP) gene and mood and anxiety disorders. A total of 21 single-nucleotide polymorphisms (SNPs) from the LSAMP gene were analyzed in 591 unrelated patients with the diagnoses of major depressive disorder (MDD) or panic disorder (PD) and in 384 healthy control subjects. The results showed a strong association between LSAMP SNPs and MDD, and a suggestive association between LSAMP SNPs and PD. This is the first evidence of a possible role of LSAMP gene in mood and anxiety disorders in humans.

Point prevalence of major depression in Estonia. Results from the 2006 Estonian Health Survey.

AIM: The study focuses on the point prevalence of major depressive episode in the Estonian population in 2006 and assesses the relationship of sociodemographic factors, health status indicators, alcohol use, and previous depressive episodes to major depression. METHODS: The present major depressive episode was assessed within the nationally representative, cross-sectional 2006 Estonian Health Survey (EHIS 2006), in which non-institutionalized individuals aged 18-84 years (n=6105) were interviewed using the Mini-International Neuropsychiatric Interview (MINI). RESULTS: The point prevalence of major depressive episode in the Estonian population was 5.6%. Depression was higher among females, in the non-Estonian ethnic group, among people older than 40 years, and in the lower-income group. CONCLUSIONS: The point prevalence of major depressive episodes was comparable with the results of other population surveys, being a little higher than the average. Age, income, ethnicity, health status, self-rated health, and previous depressive episode were independent associates of depression.

Effects of bupropion augmentation on pro-inflammatory cytokines in escitalopram-resistant patients with major depressive disorder.

Studies so far have provided contradictory results on immune system markers during use of antidepressants. There are no data on changes in immune parameters after treatment augmentation. The present study aimed to clarify whether the addition of bupropion in escitalopram-resistant patients with major depression causes changes in the immune system and whether treatment response could be predicted by baseline levels of cytokines. We recruited 28 depressive patients (11 men and 17 women) who did not respond to 12-week treatment with escitalopram (20 mg/d) for an augmentation trial with bupropion (150-300 mg/day). The levels of soluble interleukin-2 receptor, interleukin-8 (IL-8) and tumor-necrosis factor-alpha were measured before and 6 weeks after addition of bupropion. For a control group, we recruited 45 healthy volunteers (19 men and 26 women). The results indicated that the baseline levels of studied cytokines did not predict treatment response to bupropion augmentation. Concentration of IL-8 increased during the treatment similarly in both responder and non-responder groups. Although bupropion augmentation had increased the response rate in escitalopram-resistant patients, this clinical improvement was not accompanied by specific changes in studied cytokine levels.

CCK-4-induced anxiety but not panic is associated with serum brain-derived neurotrophic factor in healthy subjects.

Recent animal studies consistently confirm the involvement of brain-derived neurotrophic factor (BDNF) in the regulation of anxiety-related behaviours. The role of BDNF in human anxiety has been less investigated. The aim of our study was to examine the association between serum BDNF levels and panic/anxiety responses to cholecystokinin-tetrapeptide (CCK-4) challenge in healthy subjects. BDNF concentrations were detected in serum samples of 37 male and female volunteers before and 120 min after CCK-4 injection. The baseline levels of serum BDNF did not predict the occurrence of CCK-4-induced panic attacks or intensity of panic symptoms and did not significantly change 2 h after the challenge. BDNF serum concentrations 120 min after provocation did not differentiate panickers from non-panickers; however, the subjects reporting stronger anxiety response showed higher levels of BDNF than those with mild anxiety. The anxiety net increase on the Visual Analogue Scale, but not severity of panic symptoms, significantly and positively correlated with the change in BDNF concentration from baseline values. This is the first challenge study to demonstrate a possible impact of BDNF on human anxiety. Our findings suggest a general involvement of BDNF in the regulation of anxiety rather than a specific role of BDNF in disposition to panic attacks.

Systemic changes in body structure of 17-18-year-old schoolboys.

The purpose of this study was to assess the systemic structural changes in the body build of 17-18-year-old schoolboys in the final years of Tartu secondary schools within a height-weight classification dividing anthropometric variables into 5 SD-classes. Weight and height, 9 length, 8 breadth and 2 depth measurements, 16 circumferences and 12 skinfolds were measured. From these 5 length measurements and 53 indices were computed, which characterise the ratios of various parts of the body to body height, to upper and lower limbs' length and body composition. The subjects (n = 253) were divided into five standard deviation classes according to height and weight (Kaarma 1981, 1995). In the first three classes height and weight were proportional: (1) small height--small weight, (2) medium height--medium weight and (3) big height--big weight. In the fourth and the fifth class height and weight were non-proportional. In the fourth class weight was preponderant over height, and in the fifth class height was preponderant over weight. It was proved that a statistical difference exists between the opposite classes--the fourth and the fifth class. It was also revealed that the three proportional classes differ from each other significantly. Increase in body height and weight leads also to an increase in length, breadth and depth measurements, bone thicknesses, circumferences and skinfolds. Rohrer index, body mass index, total percentage of fat by Siri, absolute and relative mass of fat tissue increased from the small to the large class. The relationship of the length, width, and depth measurements, circumferences and bone thicknesses to height remains almost unchanged throughout the proportional classes. These investigations support the position that the whole body model may be reconstructed from body height and weight.

Ageing, soft-palate tone and sleep-related breathing disorders.

UNLABELLED: We compared the tissue tone of the soft palate in 10 young (18-29 years) and 15 middle-aged (30-70 years) apnoeics with 10 young and 10 middle-aged non-snorers and healthy volunteers of the same ages. The obstructive sleep apnoea syndrome (OSAS) was diagnosed by means of the self-reported questionnaire about the medical history of the subjects and polysomnography (PSG) with overnight pulse oximetry. Computerized endopharyngeal myotonometry (CEM) was used to measure the tissue tone of the soft palate. The CEM study is performed while the subjects are awake. CEM records and analyses the biomechanical properties of tissue in response to a brief mechanical impact. Tissue stiffness is expressed as a frequency and elasticity as a logarithmic decrement of damped oscillation. RESULTS: The values of the tissue stiffness (13.5, SD 2.5 Hz) and elasticity (1.2, SD 0.4) of the soft palate in young adults with OSAS reveal no important differences in comparison with the tissue stiffness (12.7, SD 2.4 Hz) and elasticity (0.9, SD 0.2) in non-snoring young adults. The difference in the value of the tissue stiffness of the soft palate is significant among middle-aged patients with OSAS (20.3, SD 4.7 Hz) and non-snoring middle-aged persons (13.9, SD 2.3 Hz). A non-significant difference was observed in the value of the tissue elasticity among middle-aged patients with OSAS (1.7, SD 0.8) and non-snoring middle-aged persons (1.6, SD 0.3). The tissue tone of the soft palate in young and middle-aged healthy subjects differs by elasticity but not by stiffness. CONCLUSIONS: We found that some biomechanical properties of the tissues of the soft palate may be changed by OSAS and some by age.

Course of depression: findings from cross-sectional survey in rural Udmurtia.

The aim of this study was to investigate the course of depression and to find the predictors of its chronicity and recurrence in the rural population of Udmurtia. In the sample of 232 respondents identified as having cases of unipolar depression, 21.1% had single episodes, 62.5% had recurrent episodes, and a chronic course was evident in 16.4%. Two demographic factors, Udmurt ethnicity and unmarried marital status, were significantly associated with both recurrent and chronic course of depression. A history of suicide attempt was associated only with recurrent depression; however, a trend towards a higher rate of suicide attempts was also found in the chronic depression subgroup. Factors associated only with chronic depression were poor family relationships and comorbidity with dysthymia.

Computerized endopharyngeal myotonometry (CEM): a new method to evaluate the tissue tone of the soft palate in patients with obstructive sleep apnoea syndrome.

This study compared the tissue tone of the soft palate in nonsnoring subjects and patients with obstructive sleep apnoea syndrome (OSAS) during wakefulness. Here, tissue tone means the biomechanical property of the tissue which can be characterized by two main parameters: stiffness and elasticity. Tissue tone includes both structural and neural components. A new method to evaluate the tissue tone of the soft palate was used - computerized endopharyngeal myotonometry (CEM). This method records and analyses the response of the soft palate tissues to a brief mechanical impact. The method enabled us to evaluate the most important parameters of tissue tone: stiffness, which is expressed as a frequency; and elasticity, expressed as a logarithmic decrement of the damped oscillation. First, a self-reported questionnaire was completed about the medical history of the subjects. Subjects then underwent a physical examination of the oropharynx and polysomnography with overnight pulse oximetry. The results of the CEM method indicated that patients with OSAS show an increased stiffness of the soft palate tissues (20.3, SD 4.7 Hz) compared with nonsnoring subjects (12.2, SD 1.8 Hz). In patients with sleep apnoea, elasticity is not increased in a similar way to stiffness. Thus, the disproportion between tissue stiffness and elasticity of the soft palate is a measure of the pathological changes in patients with sleep apnoea.

Cholecystokinin-induced anxiety in rats: relevance of pre-experimental stress and seasonal variations.

OBJECTIVE: To examine the influence of pre-experimental stress on the anxiogenic-like action of caerulein, an agonist of cholecystokinin (CCK) receptors. Differences in the anxiety levels of rats in summer and winter, and the role of CCK in these behavioural alterations, were also examined. DESIGN: Prospective animal study. INTERVENTIONS: Male Wistar rats were injected with the CCK agonist caerulein, or the CCK antagonists L-365,260 or devazepide, after being exposed to pre-experimental stress (handling and isolation). OUTCOME MEASURES: Performance in the plus-maze model of anxiety; serum levels of prolactin, thyrotropin and growth hormone; brain density and affinity of dopamine D2, serotonin 5-HT2 and CCK receptors. RESULTS: Caerulein (5 micrograms/kg, subcutaneous injection) caused the strongest action in animals brought to the experimental room immediately before the experiment and kept in isolation after the administration of caerulein. Caerulein did not cause any reduction of exploratory activity in rats made familiar with the experimental room and kept in the home-cage after the injection of the CCK agonist. The anti-exploratory action of caerulein in stressed rats was reversed by the CCK antagonist L-365,260 (100 micrograms/kg, intraperitoneal injection), demonstrating the involvement of the CCKB receptor subtype. In addition, seasonal fluctuations occur in the exploratory activity of rats; such activity was much lower in July than in November. The rats displaying the reduced exploratory activity had an increased number of CCK receptors in the frontal cortex and hippocampus. Simultaneously, the density of serotonin 5-HT2 receptors in the frontal cortex, but not that of dopamine D2 receptors in the striatum, was elevated. The blood level of growth hormone was also higher in July. CONCLUSIONS: The anti-exploratory action of caerulein appears to be dependent on the pre-experimental stress of rats. Moreover, the seasonal variations of exploratory behaviour of rats are evident in the plus-maze model of anxiety. The reduced exploratory activity in summer appears to be related to the elevated density of CCK and 5-HT2 receptors in the brain.

Prevalence of mood disorders in the rural population of Udmurtia.

A sample of 855 rural adult inhabitants of Udmurtia was interviewed by means of the Composite International Diagnostic Interview (CIDI) in order to investigate the incidence and prevalence of mood disorders. Depression affected 30.5% of the population according to ICD-10, and 22% according to DSM-III-R over a 12-month period. Depressive disorders were more common in women (40.5%) than in men (17.4%), and in subjects who were widowed (68.8%), divorced (55.6%) or had poor family relationships. Depression was not related to ethnicity, educational level, income or living conditions. Depression showed a high level of comorbidity with social phobia in Udmurts and with persistent somatoform pain disorder in Russian women. The annual incidence of depressive episode was 7.5%, and the highest risk of depression was among younger women and older men.

Prevalence of ICD-10 harmful use of alcohol and alcohol dependence among the rural population in Udmurtia.

A sample of 855 rural adult inhabitants in Udmurtia was interviewed by the Composite International Diagnostic Interview 1:1 (CIDI) to investigate the incidence and prevalence of alcohol-related disorders. Harmful use of alcohol and alcohol dependence affected 37.1% of the population according to ICD-10 and DSM-III-R in a lifetime period. The incidence of alcohol dependence in the previous year was 0.8% (1.4% in men, 0.4% in women). Alcohol-related disorders were more common in men (72.6%) than in women (10.3%). Correlates of alcohol dependence were sex (69.3% in men, 3.7% in women), lower education (40.1%) and being divorced in men (77.8%). Alcohol dependence had a high comorbidity with social phobia in Udmurt men and with depression in Russian men.

Effects of citalopram treatment on behavioural, cardiovascular and neuroendocrine response to cholecystokinin tetrapeptide challenge in patients with panic disorder.

Eight patients with panic disorder were administered 20 micrograms of cholecystokinin tetrapeptide (CCK-4) before and after 8 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. All patients responded to treatment by showing a significant general improvement and reaching a panic-free state for 2 weeks. At the rechallenge with CCK-4, patients displayed a marked reduction in the intensity and number of panic symptoms. The frequency of panic attacks induced with CCK-4 decreased by 50% after treatment. Citalopram treatment had no substantial effect on cardiovascular (heart rate and blood pressure) or hormonal (cortisol, prolactin and growth hormone) responses to CCK-4. Patients who still had panic attacks after treatment demonstrated a blunted growth hormone response to CCK-4 that was not seen in those who did not have panic attacks. This study suggests that treatment with an SSRI can reduce an enhanced sensitivity to CCK-4 without modifying cardiovascular and neuroendocrine responses to CCK-4 in patients with panic disorder.

The effect of cholecystokinin tetrapeptide on respiratory resistance in healthy volunteers.

The effects of cholecystokinin tetrapeptide (CCK-4) on respiratory resistance were studied in 14 healthy volunteers by the registration of slow vital capacity and flow volume loop during forced respiration test. The administration of CCK-4 (50 micrograms) was performed in a double-blind and placebo-controlled design. Injections of CCK-4 induced prominent and time-limited paniclike symptoms in all healthy volunteers. Four volunteers (29%) experienced a panic attack. Subjective dyspnea was experienced by the majority of subjects at the peak of CCK-4 effect and seemed related to a diminution in vital capacity parameters; however, the forced respiration test did not reveal bronchoconstriction after CCK-4 challenge. Administration of CCK-4 also induced a short-lasting increase in heart rate and skin blood flow. This study suggests that dyspnea induced by CCK-4 is not related to changes in respiratory resistance.

Emotional and cognitive factors connected with response to cholecystokinin tetrapeptide in healthy volunteers.

This article examines the effect of baseline anxiety, anxiety sensitivity and dysfunctional attitudes on the response to cholecystokinin tetrapeptide (CCK-4) in healthy volunteers. CCK-4 and placebo were administered to 14 subjects in a double-blind manner. Four volunteers experienced a panic attack after CCK-4 administration. Those subjects who panicked had significantly higher baseline scores on dysfunctional attitudes. Dysfunctional thought patterns appeared also to predict number of symptoms and experience of cognitive and affective symptoms during injection. Baseline anxiety as well as anxiety sensitivity predicted reactions to placebo but not panic responses to CCK-4. Results suggest that a general tendency towards erroneous interpretation of information has some role in mediating the panicogenic effects of CCK-4, and also interpersonal sensitivity may constitute a vulnerability factor for panic. Psychological factors that have been considered more specific to panic disorder, namely high state and trait anxiety as well as anxiety sensitivity, appeared mainly to determine general reactions to a threatening situation.

The effect of fluoxetine on sleep: a longitudinal, double-blind polysomnographic study of healthy volunteers.

Fluoxetine, a selective inhibitor of serotonin (5-HT) uptake, was compared with placebo in a randomized double-blind longitudinal trial in 12 healthy volunteers. Sleep polygraphic recordings were performed at home twice before and once after 6 days of medication. After 6 days fluoxetine significantly decreased the amount of rapid eye movement (REM) sleep. The sleep-onset latency and REM latency were increased, but there was no significant increase in the amount of awakenings during night. The relative proportion of stages 2 and 3 increased after fluoxetine administration, although there was no significant change with regard to total amount of slow-wave sleep. Fluoxetine did not induce prominent eye movements during non-rapid eye movement (NREM) sleep in this study. Results of the subjective assessment revealed tendencies of improved sleep and well-being in the fluoxetine group. It is concluded that a comparatively small dose of fluoxetine (20 mg/day) causes the same type of changes in REM sleep which are characteristic of most antidepressive drugs.