[Fatigue and depression]. / Fatigue et depression.

Fatigue is characterised in an overview of the literature as a specific phenomenon of depression. Its differential diagnosis is discussed. Distinctions and correspondences to burnout are elaborated. Fatigue is not an obligatory symptom of depressive episodes, although it can contribute to depressive developments. The importance of fatigue in depressive episodes and its therapy is shown with the help of a circular model of depression.

Increased self-focus in major depressive disorder is related to neural abnormalities in subcortical-cortical midline structures.

Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and reflect upon their self, which has been described as increased self-focus. Although subcortical-cortical midline structures have been associated with reflection and introspection of oneself in healthy subjects, the neural correlates of the abnormally increased attribution of negative emotions to oneself, i.e. negative self-attribution, as hallmark of the increased self-focus in MDD remain unclear. The aim of the study was, therefore, to investigate the neural correlates during judgment of self-relatedness of positive and negative emotional stimuli thereby testing for emotional self-attribution. Using fMRI, we investigated 27 acute MDD patients and compared them with 25 healthy subjects employing a paradigm that focused on judgment of self-relatedness when compared with mere perception of the very same emotional stimuli. Behaviourally, patients with MDD showed significantly higher degrees of self-relatedness of specifically negative emotional stimuli when compared with healthy subjects. Neurally, patients with MDD showed significantly lower signal intensities in various subcortical and cortical midline regions like the dorsomedial prefrontal cortex (DMPFC), supragenual anterior cingulate cortex, precuneus, ventral striatum (VS), and the dorsomedial thalamus (DMT). Signal changes in the DMPFC correlated with depression severity and hopelessness whereas those in the VS and the DMT were related to judgment of self-relatedness of negative emotional stimuli. In conclusion, we present first evidence that the abnormally increased negative self-attribution as hallmark of the increased self-focus in MDD might be mediated by altered neural activity in subcortical-cortical midline structures.

Rapid cerebral hemodynamic modulation during set shifting: evidence of time-locked associations with cognitive control in females.

Set shifting provokes specific alterations of cerebral hemodynamics in basal cerebral arteries. However, no gender differences have been reported. In the following functional transcranial Doppler study, we introduced cerebral hemodynamic modulation to the aspects of set shifting during Wisconsin Card Sorting Test (WCST). Twenty-one subjects underwent the WCST during insonation of the middle cerebral arteries. We examined gender effects on task performance and cerebral hemodynamic modulation. Further, we investigated the linkage between performance and cerebral hemodynamic modulation. In females, maximum positive modulation was restricted to the behaviorally relevant time point of set shifting, and there were time-locked associations between mental slowing during set shifting and rapid cerebral hemodynamic modulation exclusively in females. This study provides evidence of gender-related cerebral hemodynamic modulation during set shifting, and we detected time-locked brain-behavior relationship during cognitive control in females.

Deliberate self-harm in female patients with affective disorders: investigation of personality structure and affect regulation by means of operationalized psychodynamic diagnostics.

This study investigated psychodynamically relevant dimensions in female depressive patients with and without deliberate self-harm (DSH). DSH is often observed in depressive patients and frequently shows a correlation with personality disorders. Forty female depressive patients with and without DSH were investigated after recovery from acute depressive pathology by means of "operationalized psychodynamic diagnostics" (OPD). Patients with DSH had a significantly lower level of integration in the OPD dimension "structure," and their "interpersonal relationships" showed dysfunctional interaction patterns. They also had a significantly higher rate of personality disorders. These results underline the significance of aspects of personality structure in female depressive patients with DSH, and enable a deeper understanding of their dysfunctional defense strategies, the connections with underlying disturbed affect regulation, and vicious circles in the therapeutic transference-countertransference relationship. OPD has been shown to be a useful tool for empirical research into therapeutically relevant dimensions of personality.

Impaired rapid modulation of cerebral hemodynamics during a planning task in schizophrenia.

OBJECTIVE: Patients with schizophrenia show deficits in planning, and the Stockings of Cambridge (SOC) is a task that assesses planning performance. This study was undertaken to investigate rapid changes of cerebral hemodynamics during separate phases of SOC in schizophrenia and normals by means of functional transcranial Doppler sonography (fTCD). METHODS: We included 21 patients with chronic schizophrenia and a control group of 20 healthy subjects in the study. They underwent fTCD of the middle (MCA) and anterior cerebral arteries (ACA) during performance of SOC. RESULTS: The main finding was that healthy subjects significantly modulated the early cerebral hemodynamic response along distinct conditions of SOC, whereas we observed no significant differences in patients. Normally, there was an up-regulation of cerebral hemodynamics during mental planning, and about zero values were observed during movement execution. Patients showed lower development of the early cerebral hemodynamic response during planning of SOC. CONCLUSIONS: The findings of this study suggest a uniform pattern of cerebral hemodynamic regulation during a planning task in schizophrenia, whereas healthy subjects modulated such a response along a planning-movement execution sequence. SIGNIFICANCE: We provide novel evidence that modulation of cerebral hemodynamics is compromised in schizophrenia, and that fTCD constitutes a proper method to measure these alterations.

Rapid cerebral hemodynamic modulation during mental planning and movement execution: evidence of time-locked relationship with complex behavior.

OBJECTIVE: Although there is evidence of specific associations between neuronal activity and early cerebral blood flow (CBF), little is known on a logical furtherance of this linkage, namely the association between early measures of cerebral hemodynamics and complex behavior. The present study examined the linkage between hemodynamic modulation in basal cerebral arteries and performance in a non-routine planning task by means of functional transcranial Doppler sonography (fTCD). METHODS: The Stockings of Cambridge (SOC) was employed as planning paradigm. The middle and anterior cerebral arteries (MCA/ACA) were bilaterally insonated. Statistical methods comprised uni- and multivariate analyses of variance and multiple linear regression analyses. RESULTS: Taking advantage of the excellent temporal resolution of fTCD, early cerebral hemodynamic modulation of the left MCA markedly predicted task accuracy. Pronounced early blood flow increase during planning and early decrease during movement execution were associated with better performance. No such blood flow modulations were observed in worse performers. CONCLUSIONS: Early cerebral hemodynamic modulation in the left MCA proved to be a valuable neurophysiological marker that showed a great overlap with task accuracy during non-routine planning. SIGNIFICANCE: These results support the notion that a high temporal resolution in functional monitoring is a favorable strategy to disentangle relevant neurophysiological correlates of higher cognitive functioning.

Effects of psilocybin on time perception and temporal control of behaviour in humans.

Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.

Voluntary vs. involuntary hospital admission in acute mania of bipolar disorder: results from the Swiss sample of the EMBLEM study.

BACKGROUND: Patients with acute mania in bipolar disorder require pharmacological treatment to reduce symptoms. In addition, it is recognised that admission status is a clinically relevant aspect of bipolar disorder. There is, however, a lack of published data assessing the association of admission status with clinical or functional outcomes. The European-Mania-in-Bipolar-Longitudinal-Evaluation-of-Medication (EMBLEM) study has been designed to describe outcomes associated with medication therapies. Baseline data from this study are now available and we used these data to examine the characteristics of patients with acute mania in the Swiss EMBLEM cohort who were admitted involuntary and voluntary, respectively, and their functional and clinical status. METHODS: Ninety-five patients with an acutely manic or mixed episode of bipolar disorder were included in the Swiss cohort of the study. Patients' history, psychosocial functioning, clinical measures of mania and depression, pharmacological and compliance variables were assessed. Statistical methods comprised univariate analyses of variance and logistic regression analyses to elucidate associations between variables of interest. RESULTS: Patients with involuntary hospital admission (n = 55) were more aggressive and had less insight. They had a more frequent history of substance abuse and were less likely to take anticonvulsants or lithium. Furthermore, these patients showed lower compliance, which also guided physicians' decision on pharmacotherapy. LIMITATION: The EMBLEM study had an observational and non-interventional design; therefore it was not possible to compare treatment groups by means of stringent between-group analyses. However, a main target of this study was to gather clinically relevant information on outcomes of acute mania associated with currently available medication therapies. CONCLUSIONS: Involuntary admission status was significantly associated with clinical status, especially aggression and also compliance. Admission status in bipolar patients plays a clinically important role.

Association between two distinct executive tasks in schizophrenia: a functional transcranial Doppler sonography study.

BACKGROUND: Schizophrenia is a severe mental disorder involving impairments in executive functioning, which are important cognitive processes that can be assessed by planning tasks such as the Stockings of Cambridge (SOC), and tasks of rule learning/abstraction such as the Wisconsin Card Sorting Test (WCST). We undertook this study to investigate the association between performance during separate phases of SOC and WCST, including mean cerebral blood flow velocity (MFV) measurements in chronic schizophrenia. METHODS: Functional transcranial Doppler sonography (fTCD) was used to assess bilateral MFV changes in the middle (MCA) and anterior (ACA) cerebral arteries. Twenty-two patients with chronic schizophrenia and 20 healthy subjects with similar sociodemographic characteristics performed SOC and WCST during fTCD measurements of the MCA and the ACA. The SOC was varied in terms of easy and difficult problems, and also in terms of separate phases, namely mental planning and movement execution. The WCST performance was assessed separately for maintaining set and set shifting. This allowed us to examine the impact of problem difficulty and the impact of separate phases of a planning task on distinct intervals of WCST. Simultaneous registration of MFV was carried out to investigate the linkage of brain perfusion during the tasks. RESULTS: In patients, slowing of movement execution during easy problems (SOC) was associated with slowing during maintaining set (WCST) (P < 0.01). In healthy subjects, faster planning and movement execution during predominantly difficult problems were associated with increased performance of WCST during set shifting (P < 0.01). In the MCA, patients showed a significant and positive correlation of MFV between movement execution and WCST (P < 0.01). CONCLUSION: The results of this study demonstrate performance and brain perfusion abnormalities in the association pattern of two different tasks of executive functioning in schizophrenia, and they support the notion that executive functions have a pathological functional correlate predominantly in the lateral hemispheres of the brain. This study also underpins the scientific potential of fTCD in assessing brain perfusion in patients with schizophrenia.

Modulating the rate and rhythmicity of perceptual rivalry alternations with the mixed 5-HT2A and 5-HT1A agonist psilocybin.

Binocular rivalry occurs when different images are presented simultaneously to corresponding points within the left and right eyes. Under these conditions, the observer's perception will alternate between the two perceptual alternatives. Motivated by the reported link between the rate of perceptual alternations, symptoms of psychosis and an incidental observation that the rhythmicity of perceptual alternations during binocular rivalry was greatly increased 10 h after the consumption of LSD, this study aimed to investigate the pharmacology underlying binocular rivalry and to explore the connection between the timing of perceptual switching and psychosis. Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine, PY) was chosen for the study because, like LSD, it is known to act as an agonist at serotonin (5-HT)1A and 5-HT2A receptors and to produce an altered state sometimes marked by psychosis-like symptoms. A total of 12 healthy human volunteers were tested under placebo, low-dose (115 microg/kg) and high-dose (250 microg/kg) PY conditions. In line with predictions, under both low- and high-dose conditions, the results show that at 90 min postadministration (the peak of drug action), rate and rhythmicity of perceptual alternations were significantly reduced from placebo levels. Following the 90 min testing period, the perceptual switch rate successively increased, with some individuals showing increases well beyond pretest levels at the final testing, 360 min postadministration. However, as some subjects had still not returned to pretest levels by this time, the mean phase duration at 360 min was not found to differ significantly from placebo. Reflecting the drug-induced changes in rivalry phase durations, subjects showed clear changes in psychological state as indexed by the 5D-ASC (altered states of consciousness) rating scales. This study suggests the involvement of serotonergic pathways in binocular rivalry and supports the previously proposed role of a brainstem oscillator in perceptual rivalry alternations and symptoms of psychosis.

NMDA hypofunction in the posterior cingulate as a model for schizophrenia: an exploratory ketamine administration study in fMRI.

BACKGROUND: Based on animal data, NMDA receptor hypofunction has been suggested as a model for positive symptoms in schizophrenia. NMDA receptor hypofunction affects several corticolimbic brain regions, of which the posterior cingulate seems to be the most sensitive. However, empirical support for a crucial role of posterior cingulate NMDA hypofunction in the pathophysiology of positive symptoms is still missing in humans. We therefore conducted an fMRI study using the NMDA antagonist ketamine in healthy human subjects during episodic memory retrieval, which is supposed to activate the posterior cingulate. METHODS: We investigated 16 healthy subjects which were assigned to either placebo (n = 7; saline) or ketamine (n = 9; 0.6 mg/kg/h) group in a double-blind study design. All subjects received their infusion while performing an episodic memory retrieval task in the scanner. Immediately after the fMRI session, psychopathological effects of ketamine were measured using the Altered States of Consciousness Questionnaire. RESULTS: The placebo group showed BOLD signal increases in the posterior and anterior cingulate during retrieval. Signal increases were significantly lower in the ketamine group. Lower signal increases in the posterior cingulate correlated significantly with positive (i.e. psychosis-like) symptoms induced by ketamine. CONCLUSION: The present study for the first time demonstrates a relationship between NMDA receptors, posterior cingulate and positive (i.e. psychosis-like) symptoms in humans. Confirming findings from animal studies, it supports the hypothesis of a pathophysiological role of NMDA receptor hypofunction in the posterior cingulate in schizophrenia.

Lateralization of cerebral hemodynamics during Wisconsin Card Sorting Test: a functional transcranial Doppler sonography study.

OBJECTIVE: Studies on lateralization of cerebral metabolism during Wisconsin Card Sorting Test (WCST), a well-known paradigm of category learning, have shown mixed results. Moreover, sorting dimension (number, color and shape) is a cofounder of laterality in WCST. Functional transcranial Doppler sonography (fTCD) has a high temporal resolution and allows the measurement of mean cerebral blood flow velocity (CBFV) in the middle (MCA) and anterior cerebral arteries (ACA), which supply lateral and medial parts of the frontal and parietal lobes, respectively. We used fTCD to investigate CBFV changes occurring in both MCA and ACA during WCST and different sorting dimensions. METHODS: Twenty-one subjects underwent twice two distinct phases of the WCST, namely maintaining a rule (maintaining set) and searching for a new rule (set shifting), during bilateral fTCD of the MCA and ACA. RESULTS: There was a left-sided dominance of CBFV during maintaining set and set shifting in the MCA. CBFV was not associated with test performance. The sorting dimension number caused the highest CBFV increase in both MCA and ACA during maintaining set, and the sorting dimension shape caused lowest CBFV decrease in both MCA during set shifting. CONCLUSIONS: This study confirms results that cerebral blood flow (CBF) lateralizes to the left side during WCST. The 3 sorting dimensions provoked distinct processing speed during maintaining set and set shifting, but caused no effect on hemispheric lateralization. SIGNIFICANCE: Functional transcranial Doppler sonography can be used to assess CBFV during WCST and different sorting dimensions, and the latter modulate reaction time and cerebral hemodynamics.

Spatial selective attention and inhibition in schizophrenia patients during acute psychosis and at 4-month follow-up.

BACKGROUND: Attentional abnormalities may lie at the core of cognitive symptoms in schizophrenia, but it is unclear how they relate to symptoms. The major aim of our study was to understand the relation between spatial attention and clinical symptoms from acute to chronic state. METHODS: Thirty-six acutely psychotic schizophrenia patients and 42 matched control subjects were assessed on three spatial attention measures: target location detection, interference (concurrent inhibition of distractor), and negative priming (subsequent inhibition of distractor). Symptoms were assessed by the Positive and Negative Syndrome Assessment Scale. Four months later, the same subjects were re-tested, and symptoms were re-assessed. RESULTS: Symptoms were significantly reduced at the follow-up. Schizophrenia patients were slower at detecting target location than control subjects, but they improved significantly over time. Schizophrenia patients and control subjects did not differ on the interference task. Negative priming was abolished during acute psychosis, but 4 months later it was restored. Positive symptoms were correlated with reduced negative priming but not with interference, nor with target detection. Negative priming during acute psychosis was significantly correlated with the clinical symptoms at the follow-up. CONCLUSIONS: These results suggest that reduced negative priming may be associated with increased clinical, symptoms especially the positive symptoms.

Long-term course of schizophrenic illness: Bleuler's study reconsidered.

OBJECTIVE: The influential 1972 study by Manfred Bleuler on the long-term course of schizophrenic illness has been reconsidered. The authors tested the diagnosis of schizophrenia in all patients and investigated how the distribution of the types of illness course and outcome would change after exclusion of patients whose diagnosis of schizophrenia could not be confirmed by modern diagnostic standards. METHOD: Clinical charts and Bleuler's research notes on the original sample were assessed, and all patients were rediagnosed with the help of DSM-IV, DSM-III-R, ICD-10, the Research Diagnostic Criteria (RDC), Schneider's criteria, and an operationalized version of the criteria of Eugen Bleuler. RESULTS: The diagnosis of schizophrenia was not confirmed in about 30% of the sample; the majority of these patients were rediagnosed with schizoaffective disorder. High diagnostic agreement was found between DSM-IV, DSM-III-R, ICD-10, and RDC; there was much less agreement with Bleuler's and Schneider's criteria. After exclusion of patients whose schizophrenia diagnosis was not confirmed, the proportion of patients with undulating course and recovery slightly decreased, and the proportion of patients with severe end state slightly increased. Nevertheless, the distribution of the types of long-term course did not significantly change, and even among patients with strictly defined schizophrenia, half had an undulating course with remissions and 12%-15% recovered. CONCLUSIONS: Schizophrenic illness remains heterogeneous with regard to illness course and outcome even when narrowly diagnosed with the help of modern operationalized diagnostic criteria. Contemporary differentiation between schizophrenic and schizoaffective disorders is prognostically valid.

Visual object working memory function and clinical symptoms in schizophrenia.

OBJECTIVE: The presence of working memory deficits suggests abnormalities of prefrontal cortex (PFC) in schizophrenia. Although much is known about spatial working memory deficits in schizophrenia, including its potential as a phenotypic marker, it is unclear whether object working memory is similarly affected. Our goal was to examine nonspatial, object working memory function in relation to clinical symptoms. METHODS: We assessed object working memory and clinical symptoms in 28 schizophrenia patients during acute psychotic episode and 4 months later during partial remission. Delayed-matching-to-sample tasks for familiar object (DMTS-F) and novel shapes (DMTS-N) were used. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). 33 age-matched normal subjects were also tested over the same time period. RESULTS: Acutely psychotic patients showed deficits in both DMTS-F and DMTS-N. Four months later, their DMTS-F performance improved significantly but deficits in DMTS-N were still present. During acute psychosis, symptoms correlated with DMTS-F but not with the DMTS-N. Four months later, negative symptoms correlated with both tasks. CONCLUSIONS: Object working memory as measured by DMTS-N was impaired in schizophrenia patients during both acute and chronic states. When schizophrenia patients were in partial remission, object working memory was associated with negative symptoms.

Cerebral hemodynamics and processing speed during category learning.

The Wisconsin Card Sorting Test (WCST) is a commonly used paradigm of category learning with two alternating and distinct processes, maintaining set and set shifting that have been characterized by functional transcranial Doppler sonography (fTCD) of the basal cerebral arteries. Further, repeated WCST administrations resulted in improved speed of solution. This study addressed the question of whether optimised speed during maintaining set or set shifting is associated with changes of cerebral hemodynamics as measured by bilateral fTCD. During maintaining set, improved speed was associated with increased peak mean cerebral blood flow velocity (CBFV) of the anterior cerebral arteries. These results suggest a common functional substrate between optimised speed of solution and cerebral hemodynamics during maintaining set.

Early treatment-induced improvement of negative symptoms predicts cognitive functioning in treatment-naive first episode schizophrenia: a 2-year followup.

Studying neuroleptic-naive first episode schizophrenia is a strategy for investigating clinical and neuropsychological abnormalities at a very early phase of the disease without confounding influences of illness duration and medication effects. We examined the clinical and neuropsychological time course over 2 years in 32 neuroleptic-naive first episode patients (20 males, 12 females) and 21 healthy individuals with similar sociodemographic characteristics. Early treatment-induced reduction of negative symptoms predicted superior cognitive performance throughout followup in the domains of verbal fluency, attention, and non-verbal learning and memory. There were no associations between psychotic or disorganized symptoms and cognitive variables. These findings suggest an important relationship between treatment efficacy of antipsychotic medication and the longer term course of cognitive deficits in schizophrenia.

Temporal modulation of cerebral hemodynamics under prefrontal challenge in schizophrenia: a transcranial Doppler sonography study.

Transcranial Doppler sonography (TCD) is a non-invasive method to assess cerebral blood flow velocity (CBFV) and hence cerebral blood flow during cognitive activation. Major cognitive dysfunctions have been consistently reported in patients with schizophrenia, and important deficits have been observed with respect to prefrontal functions. However, prefrontal activation in schizophrenics has not been investigated with TCD despite its potential to examine short-term changes of cerebral blood flow. The Wisconsin Card Sorting Test (WCST) and the Tower of Hanoi puzzle were administered to 11 right-handed schizophrenics and 20 healthy controls. The middle and anterior cerebral arteries were pairwise insonated. Schizophrenics showed decreased CBFV during the initial phase of both prefrontal functions and the steady-state phase of the Tower of Hanoi. In healthy controls, there was a succession of three significantly different phases of mean CBFV during the Tower of Hanoi, and there was no such modulation in schizophrenics. Immediately after category shift in the WCST, there was an increase of mean CBFV in healthy controls, but not in schizophrenics. In conclusion, transcranial Doppler sonography was able to detect differing specific alterations of CBFV during two prefrontal tasks in healthy controls and patients with schizophrenia. Importantly, the results of this study imply a degraded pattern of CBFV changes over time in schizophrenia during prefrontal activation.

Eugen Bleuler and forensic psychiatry.

The list of Eugen Bleuler's writings shows that he grappled with forensic issues quite early, even before he became a full professor in 1898. Bleuler regularly prepared forensic criminal expert's reports himself until emeritus status was conferred on him in 1927. Analysis of his writings indicates that his position remained explicitly deterministic. In Bleuler's later work, that position was integrated into the natural philosophy vitalistic theory of mnemism, itself part of a more comprehensive theory, without any corrections to its content. Eugen Bleuler always remained a critic of criminal law, although it can be seen from later expert's reports that he for the most part accepted the existing system for the administration of justice for practical reasons. However, Bleuler always defended the idea that punishment should not be based on the moral guilt of the perpetrator but rather on the prospect of curing him.

Segregated neural representation of psychological and somatic-vegetative symptoms in severe major depression.

OBJECTIVE: The Beck Depression Inventory (BDI) is probably the most widely used depression scale. It has been suggested that it contains a two-factor structure measuring cognitive-affective (i.e. psychological) and somatic-vegetative depressive symptoms. In this study we aim to evaluate these factors by probing for their neural correlates. METHODS: Neural responses evoked by emotional perception, relative to an emotional judgment task, were measured using functional magnetic resonance imaging (fMRI) in 20 medication-free patients with severe MDD. Psychological and somatic-vegetative symptoms were evaluated with the BDI. RESULTS: Psychological symptoms correlated with signal changes in the dorsomedial and right ventrolateral prefrontal cortex, while somatic-vegetative symptoms correlated with signal changes in the pre-genual anterior cingulate cortex. CONCLUSIONS: These preliminary findings demonstrate segregated neural representation of psychological and somatic-vegetative symptoms of MDD in different cortical regions. Thus, our results indicate that the two-factor structure of the BDI is related to distinct neural correlates.