Minna Valkonen-Korhonen

Reality of auditory verbal hallucinations.

Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Brocas language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency.

SPECT and neuropsychological performance in severe depression treated with ECT

BACKGROUND In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT. METHODS Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT. RESULTS An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices. CONCLUSIONS Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.

Alexithymia and Tissue Inflammation

Background: Altered immune responses are seen in depression, and recent data suggest that similar changes could also be observable in alexithymia. We examined whether the inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 are independently related to alexithymia or its factors in a population-based sample. Methods: This study formed a clinical part of the Kuopio Depression (KUDEP) general population study focusing on the mental health of a general population of adults aged 25–64 years (n = 308). Alexithymia was measured using the Toronto Alexithymia Scale (TAS-20), and depressive symptoms were assessed using the Beck Depression Inventory (BDI-21). Results: The levels of IL-6 (in picograms per milliliter) and hs-CRP (in milligrams per liter) were significantly higher in alexithymic than in nonalexithymic subjects (IL-6 effect size, ES: 0.50; hs-CRP ES: 0.27). The BDI scores, hs-CRP and IL-6 explained 33.5% of the variation in TAS scores in the whole study population. According to logistic regression analysis, hs-CRP but not IL-6 increased the likelihood of belonging to the alexithymic group. This observation remained unaltered after additional adjustments for chronic inflammation-related disorders, the use of inflammation-modulating medications and depressive symptoms. Conclusions: Our findings suggest that the association between hs-CRP and alexithymia resembles that observed in depressed patients. It is, however, independent of depressive symptoms. These findings widen our view on the stress-alexithymia concept.

Midbrain serotonin and striatum dopamine transporter binding in double depression: A one-year follow-up study

Data on neurobiological differences between major depression (MD) and double depression (DD) are scarce. We examined the striatum dopamine (DAT) and midbrain serotonin transporter (SERT) binding of [123I] nor-beta-CIT in DD patients (n=8) and compared it to that in MD patients (n=11) and healthy controls (n=19). Drug-naïve patients and controls were imaged by single-photon emission computed tomography at baseline, and the patients also after one year of psychodynamic psychotherapy. Both DD and MD groups had lower midbrain [123I] nor-beta-CIT binding compared with the controls. Baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores significantly decreased in both groups after one year of psychotherapy (DD: t=3.55, p=0.009; MD: t=5.86, p<0.001). No differences between the DD and MD groups were observed in age-adjusted baseline striatum or midbrain [123I] nor-beta-CIT binding or its change during psychotherapy. Age-adjusted baseline striatum [123I] nor-beta-CIT binding correlated inversely with the duration of both dysthymia (rho=-0.76, p=0.03) and MD (rho=-0.83, p=0.01) in the DD group. No such finding was observed in the MD group (rho=0.26, p=0.44). Baseline HAM-D-17 did not correlate with the change in striatum or midbrain [123I] nor-beta-CIT binding in either group. In conclusion, our findings suggest that when using midbrain [123I] nor-beta-CIT binding as a marker of SERT binding, no differences are detectable between patients with DD and MD. However, low striatum [123I] nor-beta-CIT binding, a marker of DAT binding, may be associated with a longer illness duration in dysthymia.

Elevated levels of serum IL-5 are associated with an increased likelihood of major depressive disorder

BackgroundInflammatory mediators in both the peripheral circulation and central nervous system (CNS) are dysregulated in major depressive disorder (MDD). Nevertheless, relatively little is known about the role of the T-helper (Th)-2 effector cytokines interleukin (IL)-5 and IL-13 in MDD.MethodsWe examined the serum levels of these cytokines and a Th-1 comparison cytokine, interferon (IFN)-γ, in 116 individuals (MDD, n = 58; controls, n = 58).ResultsIn our basic multivariate model controlling for the effects of potential confounders on the associations between MDD and the examined cytokines, each 1-unit increase in the serum IL-5 level increased the likelihood of belonging to the MDD group by 76% (OR 1.76, 95% CI 1.03-2.99, p = 0.04; model covariates: age, gender, marital status, daily smoking and alcohol use). The likelihood further increased in models additionally controlling for the effects of the use of antidepressants and NSAIDS, and a diagnosis of asthma. No such associations were detected with regard to IL-13 (OR 1.08, 95% CI 0.96-1.22, p = 0.22) or IFN-γ (OR 1.02, 95% CI 0.99-1.05, p = 0.23).ConclusionsElevated levels of IL-5, which uses the neural plasticity-related RAS GTPase-extracellular signal-regulated kinase (Ras-ERK) pathway to mediate its actions in the central nervous system (CNS), could be one of the factors underlying the depression-related changes in CNS plasticity.

Analysis of galvanic skin responses with principal components and clustering techniques

An advanced method for analyzing the patterning of successive galvanic skin responses (GSR) is presented. The proposed method is based on principal component analysis in which the vector containing the measured signal is presented as a weighted sum of orthogonal basis vectors. The method is tested using measurements from 20 healthy controls and 13 psychotic patients. For each subject, 11 surprising auditory stimuli were delivered to right ear at irregular intervals and evoked GSRs were recorded from the hand. For most of the healthy controls, there was a clear pattern in successive GSRs, whereas within psychotic patients the lack of time-locking of GSRs seemed to be characteristic. These between group differences can be revealed by the proposed method. With application to clustering a significant discrimination, with overall correct ratings of 82%, of healthy controls and psychotic patients is achieved. A significant fact is that all patients were ranked correctly giving the proposed method a sensitivity of 100%.

Affective and psychotic symptoms relate to different types of P300 alteration in depressive disorder

BACKGROUND Previous findings of P300 alterations in depressive disorder have been controversial. We therefore used multivariate methods to study the relationship between P300 and affective and psychotic symptoms in depressive disorder. METHODS The P300 of 22 psychotropic drug-free depressed out-patients was registered within an auditory oddball paradigm. Affective and psychotic symptoms were evaluated using the depression and psychoticism subscales of SCL-90. The relationship of P300 amplitude and latency with affective and psychotic symptoms was assessed with multiple linear regression analysis and ANOVA. P300 values of the depressed patients were also compared with those of 22 healthy controls. RESULTS Psychotic symptoms were associated with an overall reduction in P300 amplitude, which was pronounced in the left temporocentral electrode chain (T3, C3, Cz). Psychotic symptoms were also associated with a prolonged P300 latency. Affective symptoms were associated with a relational amplitude reduction at the right temporal scalp sites. There were no statistically significant differences in P300 amplitude or latency between depressed and control-subjects. LIMITATIONS Rather small number of study subjects. The psychotic scores were low in all subjects. Multiple statistical analyses were used, and no specific a priori hypothesis was tested. CONCLUSIONS In depressive disorder, affective and psychotic symptoms are associated with different types of P300 alteration, which may indicate different underlying neurobiological processes.

Which factors are important predictors of non-recovery from major depression? A 2-year prospective observational study

Our aim was to study factors associated with long-term non-recovery from major depression. A total of 109 patients with major depression were followed prospectively for 2 years. A diagnosis of major depression based on SCID interviews at follow-up indicated non-recovery. The effect of several established risk factors was assessed. A third (30%) of the patients did not recover. Severity of initial depression were associated with poor outcome according to univariate analysis. Nevertheless, personality disorder and rural area of residence were associated with non-recovery in final multivariate analysis. Major depression in patients with personality disorder should be treated as effectively as possible. Moreover, service planning in rural areas needs attention.

Purine metabolism is dysregulated in patients with major depressive disorder

INTRODUCTION The purine cycle and altered purinergic signaling have been suggested to play a role in major depressive disorder (MDD). Nevertheless, data on this topic are scarce. Based on previous studies, we hypothesized that compared with non-depressed controls, MDD patients have distinct purine metabolite profiles. METHODS The samples comprised 99 MDD patients and 253 non-depressed controls, aged 20-71 years. Background data were collected with questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) to determine seven purine cycle metabolites belonging to the purine cycle. We investigated the levels of these metabolites in three settings: (1) MDD patients vs. non-depressed controls and (2) remitted vs. non-remitted MDD patients, and also (3) within-group changes in metabolite levels during the follow-up period. RESULTS In logistic regression adjusted for age, gender, smoking, alcohol use, physical exercise, glycosylated hemoglobin, and high-density lipoprotein cholesterol, lower levels of inosine (OR 0.89, 95% CI 0.82-0.97) and guanosine (OR 0.32, 95% CI 0.17-0.59), and higher levels of xanthine (OR 2.21, 95% CI 1.30-3.75) were associated with MDD vs. the non-depressed group. Levels of several metabolites changed significantly during the follow-up period in the MDD group, but there were no differences between remitted and non-remitted groups. CONCLUSIONS We observed altered purine metabolism in MDD patients compared with non-depressed controls. Furthermore, our observations suggest that circulating xanthine may accumulate in MDD patients.

Serum adipokine levels in adults with a history of childhood maltreatment.

Individuals with a history of childhood maltreatment present increased rates of metabolic disturbances, but the underlying mechanisms for such phenomena are poorly understood. This study examined whether the secretion of adipokines, adipocyte-derived inflammation markers closely associated with metabolic disorders, is altered in individuals with a history of childhood maltreatment. The serum levels of inflammatory markers adiponectin and resistin were measured from 147 general population participants who had a history of adverse mental symptoms, and who also reported their experiences of childhood maltreatment. Participants with experiences of childhood maltreatment (n=30) had lowered levels of serum adiponectin (p=0.007) and resistin (p=0.028). The differences in adiponectin levels persisted in multivariate modeling with adjustments for age, gender, and body mass index (OR for each 1 standard deviation decrease in the serum adiponectin level 2.65, 95% CI 1.31-5.35, p=0.007). Additional adjustments for marital status or a diagnosis of major depressive disorder, or the exclusion of individuals using NSAIDs, oral corticosteroids, or antidepressants did not alter the results. The association between resistin levels and childhood maltreatment did not remain independent in the same models. Our findings suggest that in individuals with previously reported adverse mental symptoms, a history of childhood maltreatment is independently associated with lowered levels of the anti-inflammatory marker adiponectin. This may lead to a lowered anti-inflammatory buffer capacity, which can, in turn, increase the susceptibility to physical and psychological states characterized by pronounced pro-inflammation.