Loudness dependence of auditory evoked potentials (LDAEP) in clinical monitoring of suicidal patients with major depression in comparison with non-suicidal depressed patients and healthy volunteers: A follow-up-study.

Differences in central serotonergic function due to affective disorders and due to extraordinary situations like suicidality may be visualized using the loudness dependence of auditory evoked potentials (LDAEP). Twenty patients (mean age 43.25 ± 10.85, age range 20-61, 11 male) suffering from a major depressive episode who had either acutely attempted suicide or who had suicidal plans and behavior, which are reflected by item 3 of Hamilton Depression Rating Scale ≥ 3 (suicidality), were included in the study. Furthermore, we intended to compare their LDAEP to those of non-suicidal depressed patients as well as to healthy volunteers, each matched according to age and gender. LDAEP measurement and psychometric tests took place about 2, 5, 9, 16 and 30 days after acute suicidal action or suicide attempts. In contrast to previous results, significant differences in LDAEP could not have been shown in between the suicidal group, or by comparing results of suicidal patients to non-suicidal depressed patients or to healthy volunteers. However, when the LDAEP of non-suicidal depressed patients were compared to healthy volunteers, there was a trend for a higher LDAEP in the healthy volunteers. Further studies are necessary to detect and describe further influences on serotonergic function and confounding factors like medication, smoking, age, gender, comorbidities and methods of suicidal attempts.

Cortisol, platelet serotonin content, and platelet activity in patients with major depression and type 2 diabetes: an exploratory investigation.

OBJECTIVE: Hypothalamic-pituitary-adrenal system dysfunction, serotonergic system alterations, and enhanced platelet activity may contribute to the increased cardiac risk in depression. This exploratory study examined associations between cortisol parameters, platelet serotonin (5-HT) content, and platelet activity markers in patients with newly diagnosed major depression (MD) and/or Type 2 diabetes (T2DM) compared with healthy controls. METHODS: We compared cortisol awakening response (CAR), diurnal decrease in salivary cortisol concentrations (slope), platelet 5-HT, and platelet markers (CD40, CD40 ligand [CD40L], soluble CD40L, CD62P, ß-thromboglobulin, and platelet factor-4) in 22 T2DM patients, 20 MD patients, 18 T2DM patients with MD, and 24 healthy controls. RESULTS: Platelet markers were elevated in MD (F(6,60) = 11.14, p < .001) and T2DM (F(6,60) = 13.07, p < .001). Subgroups did not differ in 5-HT or cortisol slope, whereas T2DM patients without depression had significantly lower CAR than did healthy controls (F(1,61) = 7.46, p = .008). In healthy controls, cortisol slope correlated with platelet activity for CD40 (r = -0.43, p = .048) and 5-HT was correlated with CD40L (r = 0.53, p = .007). In patients with both T2DM and MD, 5-HT and CD62P were correlated (r = 0.52, p = .033). CONCLUSIONS: Increased platelet activity in T2DM and MD may play a role in the association between diabetes, depression, and coronary artery disease. The present data suggest that group differences in cortisol or 5-HT as well as group-specific associations of cortisol or 5-HT with platelet markers might be of limited importance in the shared pathways of T2DM and depression in the pathophysiology of coronary artery disease.

The loudness dependence of auditory evoked potentials (LDAEP) as an indicator of serotonergic dysfunction in patients with predominant schizophrenic negative symptoms.

Besides the influence of dopaminergic neurotransmission on negative symptoms in schizophrenia, there is evidence that alterations of serotonin (5-HT) system functioning also play a crucial role in the pathophysiology of these disabling symptoms. From post mortem and genetic studies on patients with negative symptoms a 5-HT dysfunction is documented. In addition atypical neuroleptics and some antidepressants improve negative symptoms via serotonergic action. So far no research has been done to directly clarify the association between the serotonergic functioning and the extent of negative symptoms. Therefore, we examined the status of brain 5-HT level in negative symptoms in schizophrenia by means of the loudness dependence of auditory evoked potentials (LDAEP). The LDAEP provides a well established and non-invasive in vivo marker of the central 5-HT activity. We investigated 13 patients with schizophrenia with predominant negative symptoms treated with atypical neuroleptics and 13 healthy age and gender matched controls with a 32-channel EEG. The LDAEP of the N1/P2 component was evaluated by dipole source analysis and single electrode estimation at Cz. Psychopathological parameters, nicotine use and medication were assessed to control for additional influencing factors. Schizophrenic patients showed significantly higher LDAEP in both hemispheres than controls. Furthermore, the LDAEP in the right hemisphere in patients was related to higher scores in scales assessing negative symptoms. A relationship with positive symptoms was not found. These data might suggest a diminished central serotonergic neurotransmission in patients with predominant negative symptoms.

Newly diagnosed depression is associated with increased beta-thromboglobulin levels and increased expression of platelet activation markers and platelet derived CD40-CD40L.

BACKGROUND: Inflammation plays a key role in atherosclerotic disease. Up until now only limited evidence exists on the mechanism of cardiovascular complications in patients with depression. In addition depression was also linked to an increase in cardiovascular mortality. The present study was designed to evaluate the extent of platelet activation and platelet-derived markers of atherosclerotic disease in patients with newly diagnosed depression. METHODS: This study used whole blood aggregometry, flow cytometry and ELISA to investigate platelet CD62P (P-selectin) expression and atherosclerotic markers (CD40, CD40L) as well as serum platelet factor 4 (PF-4) and beta-thromboglobulin (ß-TG) levels in 46 participants. Patients with newly diagnosed, but not yet medically treated depression (n = 21) were compared to healthy control patients. RESULTS: The platelet activation marker CD62P was significantly higher in patients with depression (2.62% depression versus 1.27% controls; p = 0.006). Further we found basal CD40 (6.7% vs. 4.8%; p = 0.002) and basal CD40L (31.0% vs. 22.0%; p = 0.025) to be elevated in patients with depression as compared to control persons. In addition sCD40L (52.7 vs. 44.4 ng/ml; p = 0.023) and ß-TG differed significantly in depressed patients (206.9 vs. 182.8 ng/ml; p = 0.001). However, basal CD41 (97.0% vs. 96.3%; p = 0.57), CD42b (96.7% vs. 94.7%; p = 0.28) and PF-4 (89.61 vs. 81.75 IU/ml; p = 0.10) and the aggregometry results did not differ significantly between the study groups. CONCLUSIONS: Our findings with elevated CD40 and CD40L as well as CD62P and ß-TG in newly diagnosed patients emphasize that depression is linked to a prothrombotic and proinflammatory state and this possibly contributes to accelerated atherosclerosis.

New pathways of increased cardiovascular risk in depression: a pilot study on the association of high-sensitivity C-reactive protein with pro-atherosclerotic markers in patients with depression.

BACKGROUND: An elevation of inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) can be found in patients with depressive disorders. Inflammatory processes are known to influence atherosclerosis and might also mediate the link between depression and diabetes. The present study aimed at comparing hs-CRP and its relationship with atherogenic platelet markers in patients with type 2 diabetes (TD2) and/or newly diagnosed major depression (MD). METHODS: Hs-CRP concentrations in 24 patients with TD2, 21 patients with MD (diagnosed according to ICD-10 and DSM-IV), 19 patients with TD2 and comorbid MD, and 25 healthy controls were compared using analysis of variance. The relationship of hs-CRP with atherogenic platelet markers (CD40, CD40 ligand, soluble CD40L) were examined for the different samples using Pearson's correlations and regression analyses. RESULTS: Hs-CRP levels were not associated with depression (F(1, 80)=0.56, p=.814). There was a trend for higher hs-CRP in diabetes patients (p=.095), but not after adjustment for BMI. CD40 or sCD40L were not related to hs-CRP. For CD40L, regression analysis revealed a significant interaction between hs-CRP and subgroup: Hs-CRP was positively associated with CD40L only in depressed patients without diabetes (B=.334, p<.05). LIMITATIONS: Causal inferences are limited because of the cross-sectional design and the small sample size. CONCLUSIONS: Our results demonstrate preliminary evidence that hs-CRP might contribute to the risk of cardiovascular disease in depressed patients without somatic diseases via its association with platelet expression of CD40L. Further studies are necessary to confirm these findings.

Loudness dependence of auditory evoked potentials (LDAEP) in clinical monitoring of suicidal patients with major depression: a pilot study.

Loudness dependence of auditory evoked potentials (LDAEP) is a validated in vivo marker of central serotonergic function. We aimed at measuring serotonergic activity in a follow-up study of suicidal patients. It should be investigated whether suicide attempts or suicidal states cause changes in the LDAEP. Thirteen patients (mean age, 40.9 ± 11.3 years; age range, 20-61, 6 male) with a major depressive episode who had attempted suicide or had suicidal plans (Hamilton Depression Rating Scale item 3 [suicidality] ≥3) were included in the study. LDAEP and psychometric measurements took place about 2, 5, 9 and 16 days after attempted suicide or suicidal action. On day 9, LDAEP was significantly higher compared to day 2 and day 16; there was a similar tendency compared to day 5. Instability of central serotonergic function is suggested resulting in reduced serotonergic activity about 1 week after suicide attempt. Further studies are necessary that include larger samples in order to distinguish between different psychiatric diseases and to consider confounding factors like gender, smoking, medication, impulsivity or lethality of suicidal action.

The loudness dependence of auditory evoked potentials and effects of psychopathology and psychopharmacotherapy in psychiatric inpatients.

OBJECTIVE: Many studies have provided evidence for the loudness dependence of auditory evoked potentials (LDAEP) as a marker for central serotonergic activity but remained inconclusive for its suitability in clinical use. METHODS: A cross-sectional sample of 162 psychiatric inpatients (major depression N = 86, bipolar disorder N = 12, schizophrenia N = 50, and schizoaffective disorder N = 14) and 40 healthy subjects was retrospectively examined for LDAEP and effects of psychopathology and psychopharmacology. RESULTS: The LDAEP was weaker in patients with affective disorders than in healthy subjects but did not differentiate between the total patient sample and healthy controls. LDAEP correlated significantly with dimensions of the Brief Symptom Inventory in the total patient sample (depression, paranoid ideation, psychoticism, Global Symptom Index, and Positive Symptom Distress Index), in patients with affective disorders (depression) and with schizophrenia spectrum disorders (depression, psychoticism, Global Symptom Index, and Positive Symptom Distress Index). Similar correlations were found in depressed patients with a single noradrenergic and specific serotonergic antidepressant or serotonin-norepinephrine reuptake inhibitor. There was a negative correlation between dosage of typical antipsychotics and LDAEP. Hypnotics generally led to a lower LDAEP. CONCLUSION: The LDAEP in patients is related to severity of psychopathologic syndromes irrespective of diagnosis. Chronic psychopharmacologic treatment may also differentially modulate the LDAEP, but longitudinal studies are needed.

Association between wind-up ratio and central serotonergic function in healthy subjects and depressed patients.

Temporal summation of C-fiber evoked responses generates an increase in action potential discharge in second-order neurons and in perceived pain intensity (wind-up). This may be related to the central serotonergic system which modulates and partly inhibits sensory input. Aim of the study was to investigate the relationship between wind-up and serotonergic activity using loudness dependence of auditory evoked potentials (LDAEP). 18 healthy subjects were compared to 18 patients with major depression, a disease with a putative serotonin deficit. They were examined with quantitative sensory testing (QST) using the protocol of the German Research Network on Neuropathic Pain (DFNS), including the wind-up ratio (WUR), LDAEP, and psychometric measurements. We found a slight positive correlation between WUR and LDAEP both in healthy controls and depressed patients combined (r=0.340, p=0.043), indicating that WUR may be modulated by serotonergic activity. It can be concluded that inhibitory control to noxious stimuli is partly associated with the central serotonergic function as indicated by LDAEP.

1 H-MR spectroscopy in ultra-high risk and first episode stages of schizophrenia.

Using proton magnetic resonance spectroscopy biochemical characteristics in early stages of schizophrenia were examined. N-acetylaspartate, choline and creatine were measured in hippocampus, anterior cingulate gyrus (ACC) and medial prefrontal cortex (mPFC) of 24 first episode and 30 ultra-high risk patients. Careful LCModel analyses revealed no differences between the patient groups and 31 healthy controls, casting doubt upon the idea of metabolic changes in early stages of psychosis.

Serotonergic neurotransmission in early Parkinson's disease: a pilot study to assess implications for depression in this disorder.

OBJECTIVES: Depression, a disease usually accompanied by a serotonergic deficit, has been observed in about 40% of patients suffering from Parkinson's disease (PD). Thus, a serotonergic dysfunction in PD can be assumed. We aimed to investigate the interaction between serotonergic (5-HT) and dopaminergic activity in early PD. We hypothesized a serotonergic as well as a dopaminergic deficit in PD patients. We also assumed a correlation between these neurotransmitters indicating a relationship between dopaminergic and serotonergic function in PD. METHODS: Nine unmedicated PD patients before and 12 weeks after L-dopa treatment and nine healthy subjects were examined using the loudness dependence of auditory evoked potentials (LDAEP), a promising indicator of central serotonergic function. Dopaminergic transporters (DAT) were collected using (123)I-FP-CIT and single photon emission computer tomography (SPECT). LDAEP values were correlated with (123)I-FP-CIT SPECT data. RESULTS: A significant difference between LDAEP of controls and patients (P= 0.05) suggested lower serotonergic activity in PD. Twelve weeks after initiation of L-dopa treatment this difference was lost between patients and controls (P= 0.20). There was a trend towards a correlation between LDAEP and DAT (r= 0.65; P = 0.057) of the unmedicated patients, suggesting a low serotonergic activity may be related to a dopamine deficit in PD. CONCLUSIONS: Our results support the hypothesis that serotonergic neurotransmission is decreased in untreated PD and suggest that a low serotonergic activity may be related to the dopamine pathology in PD. This could be related to the high prevalence of depression in PD.

Auditory mismatch negativity deficits in long-term heavy cannabis users.

Mismatch negativity (MMN) is an auditory event-related potential indicating auditory sensory memory and information processing. The present study tested the hypothesis that chronic cannabis use is associated with deficient MMN generation. MMN was investigated in age- and gender-matched chronic cannabis users (n = 30) and nonuser controls (n = 30). The cannabis users were divided into two groups according to duration and quantity of cannabis consumption. The MMNs resulting from a pseudorandomized sequence of 2 × 900 auditory stimuli were recorded by 32-channel EEG. The standard stimuli were 1,000 Hz, 80 dB SPL and 90 ms duration. The deviant stimuli differed in duration (50 ms) or frequency (1,200 Hz). There were no significant differences in MMN values between cannabis users and nonuser controls in both deviance conditions. With regard to subgroups, reduced amplitudes of frequency MMN at frontal electrodes were found in long-term (≥8 years of use) and heavy (≥15 joints/week) users compared to short-term and light users. The results indicate that chronic cannabis use may cause a specific impairment of auditory information processing. In particular, duration and quantity of cannabis use could be identified as important factors of deficient MMN generation.

No association between chronic cannabis use and loudness dependence of auditory evoked potentials as indicator of central serotonergic neurotransmission.

Chronic cannabis use has been found to be associated with major depression. It is suggested that cannabis use induces changes in neurotransmitter systems involved in the pathogenesis of depressive disorders, particularly in the serotonergic system. The analysis of the loudness dependence of auditory evoked potentials (LDAEP) is a valid non-invasive indicator of central serotonergic activity in animals and humans. In the present study, we investigated the effects of chronic cannabis use on LDAEP in 30 psychiatrically unaffected users compared to 30 non-user controls. Users were required to abstain from cannabis for at least 24 h before testing. Putative depressive symptoms were assessed by using the Beck Depression Inventory (BDI) and the Hamilton Rating Scale for Depression (HAMD-21). LDAEP as well as BDI and HAMD-21 scores did not differ between cannabis users and controls. Moreover, LDAEP neither correlate with duration and quantity of cannabis use nor with psychometric assessments. These results indicate that chronic cannabis use had no influence on the LDAEP in this study sample. It can be suggested that significant alterations in serotonergic systems may rather be related to acute activation of the endogenous cannabinoid system or to cannabis dependence accompanied by manifest depressive symptoms.

Serotonergic dysfunction in the prodromal, first-episode and chronic course of schizophrenia as assessed by the loudness dependence of auditory evoked activity.

Recent studies revealing evidence of increased serotonergic neurotransmission in schizophrenia has generated substantial interest in the role of serotonin in its pathophysiology. None of these studies, however, have queried whether dysfunctional serotonergic activity might already have been present in subjects of at-risk mental state for schizophrenia before the onset of psychotic symptoms, and whether serotonergic activity further increases during the development of schizophrenia and the chronic course. Although no valid indicator for measuring the activity level of serotonergic neurotransmission has yet been found, a series of evidence from human and animal studies suggests that a weak loudness dependence of auditory evoked potentials (LDAEP) indicates high serotonergic activity and vice versa. We examined the LDAEP (N1/P2 component) in 60 patients with at-risk mental state for schizophrenia who showed characteristic prodromal symptoms, 34 first-episode patients, 28 patients with a chronic course of schizophrenia and 57 healthy controls. Prodromal patients showed significantly weaker LDAEP in comparison to healthy volunteers, but similarly to that in first-episode and chronic patients. None of the covariates such as age, gender, medication, age of onset, or psychopathology had an influence on this finding. In a subsample of prodromal patients, LDAEP values remain the same after retesting 10 months later. These results indicate that serotonergic neurotransmission had already increased before the onset of the full-blown psychosis of schizophrenia and remains enhanced in the further course of the disease. A weak LDAEP may therefore represent a vulnerability marker rather than an expression of illness progression.

Psychosurgery and deep brain stimulation as ultima ratio treatment for refractory depression.

For decades, the most severe, protracted and therapy-resistant forms of major depression have compelled clinicians and researchers to look for last resort treatment. Early psychosurgical procedures were hazardous and often associated with severe and persistent side effects including avolition, apathy and change of personality. With the introduction of psychopharmacological treatments in the 1950s, the frequency of ablative procedures declined rapidly. The past decade, however, has witnessed the resurgence of surgical strategies as a result of refined techniques and advances such as high frequency stimulation of deep brain nuclei. Recent data suggest that the overall effect of high frequency stimulation lies in the functional inhibition of neural activity in the region stimulated. Contrary to other psychosurgical procedures, high frequency stimulation reversibly modulates targeted brain areas and allows a postsurgical adaption of the stimulation parameters according to clinical outcome. With increased understanding of the brain regions and functional circuits involved in the pathogenesis of psychiatric disorders, major depression has emerged as a target for new psychosurgical approaches to selectively and precisely modulate neural areas involved in the disease process. Recent studies of minimally intervening procedures report good clinical outcome in the treatment of therapy-resistant forms of major depression. High frequency stimulation was successfully applied in several small samples of patients with treatment-resistant depression when the stimulation focused on different areas, e.g., nucleus accumbens, the lateral habenula or cortical areas. Nevertheless, the reticence toward psychosurgery, even for those patients suffering from the most debilitating forms of depression, still prevails, even though recent studies have shown significant improvement in terms of quality of life with the limitation that the number of treated cases has been small. In any event, valid and unambiguous criteria for patient eligibility have yet to be refined and standardized. In this review, we suggest possible standard criteria for the application of deep brain stimulation on patients suffering from otherwise treatment-resistant depression.

Validation of the Personal and Social Performance (PSP) Scale in a German sample of acutely ill patients with schizophrenia.

In trying to more broadly define outcome in the efficient long-term treatment of patients with schizophrenia it is necessary to consider not only a reduction in psychopathological symptoms but also a successful psychosocial reintegration. Thus, a more exact assessment of psychosocial functioning is needed. Since the GAF (Global Assessment of Functioning) scale and the SOFAS (Social and Occupational Functioning Assessment Scale) are less operationalized and confuse psychosocial facts with psychopathological symptoms, the Personal and Social Performance (PSP) scale was developed [Morosini, P.L., Magliano, L., Brambilla, L., Ugolini, S., Pioli, R. (2000). Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatrica Scandinavica, 1001, 323-329.] containing the four main areas "socially useful activities, personal and social relationships, self-care, as well as disturbing and aggressive behaviour". Validation of the PSP scale was conducted in a sample of 62 patients with acute schizophrenia. Rating instruments were PSP, GAF, SOFAS, PANSS, CGI, and Mini-ICF-P (Mini-ICF-Rating for Mental Disorders). The results showed good reliability with alpha=.64-.84, high test-retest reliability as well as good inter-rater reliability for the PSP scale. Furthermore, PSP proved good validity with high correlations to GAF (r=.91), SOFAS (r=.91), and Mini-ICF-P (r=-.69). The hypothesis that more critically ill patients would show lower scores on PSP than lesser ill patients was only confirmed for PANSS negative symptoms. Thus, the findings prove the PSP scale to be a reliable and valid instrument for assessing social functioning of patients with schizophrenia during the course of treatment as well as in the acute state.

Reduction of auditory event-related P300 amplitude in subjects with at-risk mental state for schizophrenia.

Neurophysiological methods allow the examination of cognitive-cortical functioning in patients with schizophrenia in its prodromal states. As revealed by previous studies, event-related potential components such as auditory evoked P300 associated with cognitive processes, such as attention and orientation, are known to be reduced in amplitude in acute and chronic as well as in medicated and unmedicated patients. It is, however, unclear whether a P300 amplitude reduction occurs before the schizophrenic psychosis is fully manifested. We studied patients in the prodromal phase of the schizophrenic disorder (i.e. subjects with an at-risk mental state showing attenuated psychotic symptoms or brief limited intermittent symptoms) as well as first-episode patients and chronic patients with schizophrenia and compared these groups to healthy subjects. The event-related P300 was recorded during an auditory oddball paradigm. Groups differed significantly from each other in the P300 amplitude at Pz (F(3/149)=2.532, p=0.02). Post-hoc tests revealed significantly lower P300 amplitudes of non-medicated prodromal (p=.03), first-episode (p=.01) and chronic patients (p=.001) compared to the healthy controls. The study revealed that there are neurophysiological changes as the reduction in P300 amplitudes begins early in schizophrenia at the prodromal phase, i.e. before a manifestation of full-blown psychosis, and that these changes seem to have a progressive course from prodromal to chronic state of schizophrenia as assumed in this cross-sectional study.

Loudness dependence of auditory evoked potentials as indicator of central serotonergic neurotransmission: simultaneous electrophysiological recordings and in vivo microdialysis in the rat primary auditory cortex.

Serotonin released in synapsis is one of the key neurotransmitters in psychiatry and psychopharmacology. The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a marker for central serotonergic neurotransmission. Several findings in animals and humans support this hypothesis. However, the in vivo measurement of cortical extracellular serotonin levels has never been performed simultaneously with the recording of auditory evoked potentials. The interrelationship between low cortical serotonergic activity and strong LDAEP is yet to be proven. The auditory evoked potentials were recorded in the epidura above the primary auditory cortex of male Wistar rats whereas extracellular serotonin levels in the primary auditory cortex were measured by in vivo microdialysis before and after i.p. application of the selective serotonin reuptake inhibitor citalopram. At baseline, the correlation of coefficients between the LDAEP, especially of the N1 component, and extracellular serotonin levels in the primary auditory cortex was negative. The increase of serotonin levels after citalopram application was significantly related to a decrease of LDAEP of the N1 component (r=-0.86, p=0.003). These data support the view that the LDAEP is closely modulated by cortical serotonergic activity. Thus, the LDAEP might serve as an inversely related marker of synaptically released serotonin in the CNS.

Association of 5-HT1B receptor polymorphisms with the loudness dependence of auditory evoked potentials in a community-based sample of healthy volunteers.

The terminal autoreceptor 5-HT1B is centrally involved in the regulation of the brain serotonergic system and in several psychiatric disorders including depression, addiction, and obsessive-compulsive disorder. The loudness dependence of the auditory evoked N1/P2-component (LDAEP; primary auditory cortex) is currently considered as one of best-validated indicators of serotonergic neurotransmission, especially for synaptically released serotonin. Since the 5-HT1B receptor is involved in the release of serotonin at terminal endings of cortical neurons, this study addressed the question whether single nucleotide polymorphism (SNP) in the gene coding for this receptor (HTR1B) are related to LDAEP of the primary auditory cortex (tangential dipole) investigating a community-based sample of 127 healthy subjects randomly selected from the general population. In this carefully recruited sample, a G-G haplotype (rs1213368-rs6296) and the respective G-alleles were found to be related to a strong LDAEP response of the left tangential dipole, indicating low serotonergic activity. Apart from the fact that this is the first study which relates HTR1B SNPs to a measure of serotonergic function, it can be speculated that LDAEP may reflect parts of the release mechanism of serotonin at cortical synapses, although the lateralized finding cannot be entirely explained. Carriers of the G-alleles may be characterized by a particularly strong feedback inhibition of serotonin release at cortical terminals in the primary auditory cortex, possibly mediated by higher sensitivity of 5-HT1B receptors associated with low serotonergic activity.

Loudness dependence of the auditory evoked N1/P2 component as an indicator of serotonergic dysfunction in patients with schizophrenia--a replication study.

Serotonergic dysfunction appears to be involved in the pathogenesis of schizophrenia. The loudness dependence of auditory evoked potentials (LDAEP) has been suggested to be a valid indicator of the brain serotonin system's activity in humans. Patients with schizophrenia showed weaker LDAEP, indicating high serotonergic activity, in comparison to healthy controls. Thus, we were able again to demonstrate electrophysiological evidence for an upregulated serotonergic system in schizophrenia.