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Biomedical subjects

C Lorenzi

Publications and source records attributed to C Lorenzi.

At least 37 records · Page 2Linked to original sources

Serotonin-2C and serotonin-1A receptor genes are not associated with psychotic symptomatology of mood disorders.

The serotonergic system is involved in both pathophysiology and treatment of mood disorders. In the present study we investigated the possible influence of the polymorphisms of the serotonin-1A and 2C receptor genes on the symptomatology of mood disorders. Eighty-four inpatients affected by mood disorders (72 bipolar and 12 major depressive disorder) were assessed by the Operational Criteria Checklist for Psychotic Illness to score their lifetime psychotic symptomatology. The subjects were also typed for 5HT1A and 5HT2C variants using polymerase chain reaction techniques. No association was found between 5HT2C and psychopathology as defined by the four symptomatologic factors used as phenotype definition (mania, depression, delusion, and disorganization) even when bipolar subjects were analyzed separately. Only one subject with the 5HT1A variant was observed. Genetic variation at the 5HT1A and 5HT2C receptor genes does not, therefore, play a major role in the pathogenesis of mood disorders symptomatology. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:161-166, 2000.

Adult↗

Serotonin-2A receptor gene is not associated with symptomatology of schizophrenia.

The serotonin receptor type 2A (5-HT2A) is a primary candidate for involvement in major psychoses. Polymorphisms within the 5-HT2A gene have recently been reported to be associated with a variety of psychopathological conditions. In the present study, we investigated the potential influence of the T102C polymorphism on the psychopathology of schizophrenia. One hundred eighty-eight inpatients affected by schizophrenia (DSM-III-R) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were typed for their 5-HT2A variants by PCR techniques. Mania, depression, delusion and disorganization were the four symptomatologic factors previously derived from our psychotic population that were used to define phenotype in our sample. Genetic variants of the polymorphism under study were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex and age of onset did not reveal any association either. Our results do not, therefore, support the hypothesis that the serotonin receptor 2A gene is a liability factor for the symptomatology of schizophrenia as defined by the OPCRIT checklist. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:84-87, 2000.

Adult↗

Visual sensitivity to temporal modulations of temporal noise.

The present endeavor is meant (a) to provide a direct comparison between first- and second-order temporal modulation and, by so doing, (b) to eliminate all spatial clues that might have contaminated previous assessments of the second-order temporal modulation transfer function (TMTF). The second aim was achieved by means of the temporal modulation of a purely temporal white noise, a stimulus used frequently in psychoacoustics but not used as yet in visual stimulation. Luminance and contrast temporal modulation thresholds were measured with a 2AFC staircase procedure. In the first case, the mean luminance of a spatially homogeneous, 30 degrees field was modulated sinusoidally over time (first-order modulation). In the second case, the luminance of the same or of a 60 degrees field was randomized over time at a rate of 150 Hz and this temporal white noise (the carrier) was modulated sinusoidally over time (second-order modulation). First-order thresholds reproduce the classical (large field) flicker sensitivity. Second-order thresholds (measured for the first time with purely temporal stimuli) are at least 100 times higher than first-order ones, display a low-pass characteristic (at least up to 0.5 Hz) and yield a critical fusion frequency (measured at 100% modulation) of approximately 10 Hz. The data are in accord with other estimates of the TMTF of the second-order system and thus confirm the effective neutralization of the spatial cues present in these previous studies.

Adult↗

Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and disorganization symptomatology in major psychoses.

The D2 receptor (DRD2) is a binding site of many psychoactive drugs and it has been proposed as a genetic risk factor for psychiatric disorders. The aim of this investigation was to study the DRD2 S311C variant in major psychoses. We studied 1182 inpatients with diagnoses of bipolar disorder (n = 480), major depressive disorder (n = 269), schizophrenia (n = 366), delusional disorder (n = 44), psychotic disorder not otherwise specified (n = 23) and 267 healthy controls. Eight hundred and eighty-seven subjects were also scored for their lifetime symptomatology using the the Operational Criteria checklist for psychotic illness (OPCRIT). DRD2 variants were not associated with affected subjects even when possible confounders like gender and onset were considered. When we considered the 887 subjects with the symptomatologic analysis, we observed a significant association of the DRD2 S311C variant with both delusion and disorganization features. The association was present independently from diagnoses. Our results do not show that coding variants of the DRD2 S311C play a major role in conferring susceptibility to major psychoses, but they may be connected with disorganized and delusional symptomatology independently from diagnoses.

Adult↗

Use of temporal envelope cues by children with developmental dyslexia.

This study evaluates the ability to process auditory temporal-envelope cues in a group of 6 children with dyslexia (mean age: 10;10 years;months). To address this issue, we measured (a) temporal modulation transfer functions (TMTFs), that is, the detection thresholds of sinusoidal amplitude modulation (SAM) applied to a white noise carrier, as a function of modulation frequency, fm (fm was 4, 16, 64, 256, and 1,024 Hz) and (b) identification performance for vowel-consonant-vowel (VCV) stimuli over 5 sessions. VCV stimuli were either unprocessed or digitally processed to remove the original spectral information, resulting in a time-varying speech envelope amplitude modulating a noise carrier. The same tests were conducted in 6 normal control children (mean age: 11;6 years;months) and 6 normal control adults (mean age: 24;8 years;months). SAM thresholds were similar in normal children and adults. For both normal groups, TMTFs were low pass in shape and showed low between-listener variability. TMTFs measured in children with dyslexia showed higher between-listener variability: TMTFs were band pass in 2 children, flat in 1 child, and low pass in the 3 others. Overall, SAM thresholds were higher in children with dyslexia than in normal children at fm = 4 and 1,024 Hz. Unprocessed-speech identification performance was nearly perfect in normal children and adults, and impaired in children with dyslexia. "Speech-envelope noise" identification performance was poorer in normal children and children with dyslexia than in normal adults. Performance improved across sessions in normal children and adults, but remained constant in children with dyslexia. Compared to normal children, children with dyslexia showed poorer reception of voicing, manner, and place of articulation for unprocessed speech and poorer reception of voicing for "speech-envelope noise." Taken together, these results support the hypothesis that some children with dyslexia may show abnormal auditory temporal-envelope processing. Such a deficit, in turn, may explain the difficulties of children with dyslexia with speech perception.

Adolescent↗

Representation of the temporal envelope of sounds in the human brain.

The cerebral representation of the temporal envelope of sounds was studied in five normal-hearing subjects using functional magnetic resonance imaging. The stimuli were white noise, sinusoidally amplitude-modulated at frequencies ranging from 4 to 256 Hz. This range includes low AM frequencies (up to 32 Hz) essential for the perception of the manner of articulation and syllabic rate, and high AM frequencies (above 64 Hz) essential for the perception of voicing and prosody. The right lower brainstem (superior olivary complex), the right inferior colliculus, the left medial geniculate body, Heschl's gyrus, the superior temporal gyrus, the superior temporal sulcus, and the inferior parietal lobule were specifically responsive to AM. Global tuning curves in these regions suggest that the human auditory system is organized as a hierarchical filter bank, each processing level responding preferentially to a given AM frequency, 256 Hz for the lower brainstem, 32-256 Hz for the inferior colliculus, 16 Hz for the medial geniculate body, 8 Hz for the primary auditory cortex, and 4-8 Hz for secondary regions. The time course of the hemodynamic responses showed sustained and transient components with reverse frequency dependent patterns: the lower the AM frequency the better the fit with a sustained response model, the higher the AM frequency the better the fit with a transient response model. Using cortical maps of best modulation frequency, we demonstrate that the spatial representation of AM frequencies varies according to the response type. Sustained responses yield maps of low frequencies organized in large clusters. Transient responses yield maps of high frequencies represented by a mosaic of small clusters. Very few voxels were tuned to intermediate frequencies (32-64 Hz). We did not find spatial gradients of AM frequencies associated with any response type. Our results suggest that two frequency ranges (up to 16 and 128 Hz and above) are represented in the cortex by different response types. However, the spatial segregation of these two ranges is not systematic. Most cortical regions were tuned to low frequencies and only a few to high frequencies. Yet, voxels that show a preference for low frequencies were also responsive to high frequencies. Overall, our study shows that the temporal envelope of sounds is processed by both distinct (hierarchically organized series of filters) and shared (high and low AM frequencies eliciting different responses at the same cortical locus) neural substrates. This layout suggests that the human auditory system is organized in a parallel fashion that allows a degree of separate routing for groups of AM frequencies conveying different information and preserves a possibility for integration of complementary features in cortical auditory regions.

Acoustic Stimulation↗

Measurement of the temporal-modulation transfer function for a single listener with cochlear hearing loss and left-hemisphere damage.

The modulation depth required for the detection of sinusoidal amplitude-modulation applied to a white noise carrier was measured as a function of modulation frequency, giving temporal modulation transfer functions (TMTFs). Five adult listeners with normal hearing (mean age 52 years), five elderly listeners with moderate cochlear hearing loss (mean age 66 years) and a single elderly listener (aged 73 years) with moderate cochlear hearing loss and left-hemisphere damage were tested in the right ear at 50 dB SL. The five elderly listeners were matched in audiogram with the brain-damaged listener. Modulation detection was systematically poorer than normal in the five elderly listeners with cochlear hearing loss. However, their TMTFs were lowpass in shape, as for the five normal-hearing adult listeners. Modulation detection was much poorer in the elderly listener with cochlear hearing loss and left-hemisphere damage compared to the five normal-hearing adults and the five elderly listeners with cochlear hearing loss. Moreover, modulation detection was poorer at 4, 64 and 128 Hz than at 8, 16 and 32 Hz in the brain-damaged listener, giving his TMTF a bandpass appearance. These results are in agreement with the hypothesis that the main factors limiting the ability to detect changes in the temporal-envelope of sounds are located at a central (retro-cochlear) level of the auditory system rather than at a peripheral (cochlear) level. They also suggest that the TMTF approach may prove useful in distinguishing peripheral and central hearing losses.

Aged↗

Dopamine receptor D4 is not associated with antidepressant activity of sleep deprivation.

Total sleep deprivation (TSD) is an effective treatment for mood disorders which is thought to act through an enhancement in several neurotransmitter pathways including dopaminergic transmission. However, not all patients respond to TSD and genetic factors are likely to play a major role in determining TSD response. The aim of this study is to investigate the influence of dopamine receptor D4 exon 3 (DRD4) variants on TSD antidepressant efficacy in bipolar disorder. One hundred and twenty-four depressed inpatients affected by bipolar disorder (DSM-IV) were treated with repeated cycles of TSD and were typed for DRD4 variants at the third exon using polymerase chain reaction (PCR) techniques. DRD4 variants were not associated with TSD outcome. Consideration of possible stratification effects such as gender, age at onset and duration of illness did not reveal any association either. DRD4 exon 3 variants are not a main factor influencing TSD outcome in bipolar disorder.

Alleles↗

Dopamine D3 receptor gene not associated with symptomatology of major psychoses.

Dopamine D3 receptor gene (DRD3) variants have been implicated in the pathogenesis of psychiatric disorders. Many studies, however, have failed to replicate the association of DRD3 with schizophrenia. A possible reason for this may lie in the definition of phenotype, which is traditionally based on psychiatric diagnosis. In this study we investigated the possibility that variants of the DRD3 gene might be associated with symptomatology in a sample of subjects affected by major psychoses. Two hundred and eleven inpatients affected by major psychoses were assessed by the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and were also typed for the DRD3 variants using polymerase chain reaction techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definitions. DRD3 variants were not associated with these symptomatologic factors, and consideration of possible stratification effects, such as sex and psychiatric diagnosis, did not reveal any association either.

Adolescent↗

No interaction between serotonin transporter gene and dopamine receptor D4 gene in symptomatology of major psychoses.

Previously, we reported an association of the dopamine receptor D4 (DRD4) gene with delusional symptomatology of major psychoses. However, DRD4 variants accounted for only 2% of the phenotypic variance, indicating that contributions from other genes were probable. The serotonin transporter gene is a primary candidate in major psychoses, and a functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has recently been reported to be associated with a number of psychopathological conditions. In the present study we investigated the original cohort of subjects to evaluate the 5-HTTLPR possible influence on the psychopathology of major psychoses in interaction with DRD4. Four hundred and sixty-one inpatients affected by major psychoses were assessed by the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and were also typed for the 5-HTTLPR and DRD4 variants using polymerase chain reaction techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definition. 5-HTTLPR variants did not significantly influence the previously reported association of DRD4 with delusional symptoms. No interaction was observed on the other symptom factors. The serotonin transporter gene does not, therefore, interact with DRD4 in determining the symptomatology of major psychoses.

Adolescent↗

Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes and response to lithium prophylaxis in mood disorders.

Lithium is an effective prophylactic agent in mood disorders, and genetic factors are likely to modulate individual susceptibility to lithium treatment. The aim of this study is to investigate the influence of dopamine receptor D2 (DRD2), D4 exon 3 (DRD4), and gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1) gene variants on the efficacy of lithium prophylaxis in mood disorders. Patients with mood disorders (N = 125: bipolar subtype, n = 100; major depressive disorder subtype, n = 25) were followed prospectively for an average of 53 months and were typed for DRD2 (Ser311/Cys311: n = 121, VNTR: n = 63), DRD4 (n = 125) and GABRA1 (n = 61) variants using polymerase chain reaction (PCR) techniques. DRD2, DRD4 and GABRA1 variants were not associated with response to lithium. A trend was observed toward a better outcome of DRD4* 2/4 subjects, but it was due to only two subjects. Consideration of possible stratification effects like gender, polarity, family history, age at onset and duration of lithium treatment did not reveal any association either. DRD2, DRD4 and GABRA1 variants therefore do not appear to be associated with the outcome of lithium prophylaxis in mood disorders.

Adult↗

No association between serotonin-2A receptor gene polymorphism and psychotic symptomatology of mood disorders.

Abnormalities of the serotonergic system are involved in the pathophysiology of mood disorders. In the present study, we investigated the possible influence of the T102C polymorphism of the serotonin-2A receptor gene (5-HT2A, 13q14-21) on the symptomatology of mood disorders. Inpatients affected by mood disorders (n = 246, 149 bipolar, 97 major depressive disorder) were assessed with a checklist of operational criteria for psychotic illness (OPCRIT) to score their lifetime psychotic symptomatology. The subjects were also typed for 5-HT2A variants using polymerase chain reaction techniques. No association was found between this polymorphism and psychopathology as defined by the four symptomatologic factors used in phenotype definition (mania, depression, delusion and disorganization). Genetic variation at the 5-HT2A receptor gene does not, therefore, appear to play a major role in the pathogenesis of major mood disorders.

Adult↗

Effects of envelope expansion on speech recognition.

This study investigated the effects of expanding the gross time-amplitude variations of 'speech-envelope noise' stimuli on speech recognition. The initial stimuli were VCV logatomes presented in quiet or against a steady white noise with a 0-dB signal-to-noise ratio. Their low-frequency temporal modulations (<500 Hz) were extracted in broad frequency bands, and raised to the power 2. The resulting envelopes were then used to modulate a white noise, and combined to produce the 'speech-envelope noise' stimuli. As a consequence, listeners were forced to identify speech using primarily temporal envelope cues. The results obtained with four normal-hearing listeners show small decrements in recognition performance of 1-15% when expanding the envelope of the speech stimuli presented in quiet. The results also show a small but consistent improvement in performance of 6-14% when expanding the envelope of the speech stimuli presented in noise. These results are consistent with those obtained by Fu and Shannon (J. Acoust. Soc. Am. 104 (1998) 2570-2577) with speech presented in quiet. They also suggest that the reduction in the modulation depth of the speech envelope caused by noise or reverberation could be compensated by expanding low-frequency temporal modulations.

Adult↗

Sound localization in noise in hearing-impaired listeners.

The present study assesses the ability of four listeners with high-frequency, bilateral symmetrical sensorineural hearing loss to localize and detect a broadband click train in the frontal-horizontal plane, in quiet and in the presence of a white noise. The speaker array and stimuli are identical to those described by Lorenzi et al. (in press). The results show that: (1) localization performance is only slightly poorer in hearing-impaired listeners than in normal-hearing listeners when noise is at 0 deg azimuth, (2) localization performance begins to decrease at higher signal-to-noise ratios for hearing-impaired listeners than for normal-hearing listeners when noise is at +/- 90 deg azimuth, and (3) the performance of hearing-impaired listeners is less consistent when noise is at +/- 90 deg azimuth than at 0 deg azimuth. The effects of a high-frequency hearing loss were also studied by measuring the ability of normal-hearing listeners to localize the low-pass filtered version of the clicks. The data reproduce the effects of noise on three out of the four hearing-impaired listeners when noise is at 0 deg azimuth. They reproduce the effects of noise on only two out of the four hearing-impaired listeners when noise is at +/- 90 deg azimuth. The additional effects of a low-frequency hearing loss were investigated by attenuating the low-pass filtered clicks and the noise by 20 dB. The results show that attenuation does not strongly affect localization accuracy for normal-hearing listeners. Measurements of the clicks' detectability indicate that the hearing-impaired listeners who show the poorest localization accuracy also show the poorest ability to detect the clicks. The inaudibility of high frequencies, "distortions," and reduced detectability of the signal are assumed to have caused the poorer-than-normal localization accuracy for hearing-impaired listeners.

Aged↗

Sound localization in noise in normal-hearing listeners.

The ability to localize a click train in the frontal-horizontal plane was measured in quiet and in the presence of a white-noise masker. The experiment tested the effects of signal frequency, signal-to-noise ratio (S/N), and masker location. Clicks were low-pass filtered at 11 kHz in the broadband condition, low-pass filtered at 1.6 kHz in the low-pass condition, and bandpass filtered between 1.6 and 11 kHz in the high-pass condition. The masker was presented at either -90, 0, or +90 deg azimuth. Six signal-to-noise ratios were used, ranging from -9 to +18 dB. Results obtained with four normal-hearing listeners show that (1) for all masker locations and filtering conditions, localization accuracy remains unaffected by noise until 0-6 dB S/N and decreases at more adverse signal-to-noise ratios, (2) for all filtering conditions and at low signal-to-noise ratios, the effect of noise is greater when noise is presented at +/- 90 deg azimuth than at 0 deg azimuth, (3) the effect of noise is similar for all filtering conditions when noise is presented at 0 deg azimuth, and (4) when noise is presented at +/- 90 deg azimuth, the effect of noise is similar for the broadband and high-pass conditions, but greater for the low-pass condition. These results suggest that the low- and high-frequency cues used to localize sounds are equally affected when noise is presented at 0 deg azimuth. However, low-frequency cues are less resistant to noise than high-frequency cues when noise is presented at +/- 90 deg azimuth. When both low- and high-frequency cues are available, listeners base their decision on the cues providing the most accurate estimation of the direction of the sound source (high-frequency cues). Parallel measures of click detectability suggest that the poorer localization accuracy observed when noise is at +/- 90 deg azimuth may be caused by a reduction in the detectability of the signal at the ear ipsilateral to the noise.

Adult↗

Amplitude compression in cochlear implants artificially restricts the perception of temporal asymmetry.

This paper presents a study in which five cochlear implantees were asked to discriminate the timbre of stimuli with temporally asymmetric envelopes. Stimuli were damped and ramped sinusoids presented acoustically. They were transformed by the speech processor of the implant and were presented through one electrode. All cochlear implantees could discriminate the damped and ramped sinusoids when the half-life was 4 ms, the carrier frequency was 400 Hz, and the period of the envelope was 50 ms. In a second experiment, timbre discrimination performance was measured as a function of half-life for two cochlear implantees. Both showed that timbre discrimination was possible over the range 1-24 ms. In normal-hearing listeners, the range is 1-64 ms and in cochlear implantees, stimulated directly without the speech processor, the range is 1-300 ms. At long half-lives, the decrease in discrimination performance observed with the speech processor appears to be due to the amplitude compression applied by the device. The present results suggest that it may be important to ensure that cochlear implants do not restrict temporal asymmetry unduly when applying compression to control level.

Adult↗