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Biomedical subjects

C Lorenzi

Publications and source records attributed to C Lorenzi.

At least 19 recordsLinked to original sources
PubMed2002

Serotonin transporter gene (5-HTTLPR) and major psychoses.

Serotoninergic neurotransmitter systems have been implicated in the pathogenesis of major psychoses. A functional polymorphism (5-HTTLPR) in the upstream regulatory region of the gene (SLC6A4) has been associated with a number of psychiatric disturbances, but conflicting replication followed. The aim of this study was to investigate the possibility that the 5-HTTLPR might be associated with major psychoses. One thousand, eight hundred and twenty inpatients (789 bipolars, 667 major depressives, 66 delusionals, 261 schizophrenics, 37 psychotics not otherwise specified-NOS) and 457 control subjects were included in this study. A subsample of 1235 patients (523 bipolars, 359 major depressives, 259 schizophrenics, 66 delusionals, 28 psychotic NOS) were evaluated for lifetime psychotic symptomatology using the Operational Criteria for Psychotic illness (OPCRIT) checklist. The subjects were also typed for 5-HTTLPR variants using PCR techniques. 5-HTTLPR allele frequencies were not significantly different between controls and bipolars, major depressives, schizophrenics, delusionals and psychotic NOS; genotype analysis also did not show any association. The analysis of symptomatology did not show significant differences. Consideration of possible stratification factors such as sex and age of onset did not significantly influence results. 5-HTTLPR variants are not therefore a liability factor for major psychoses or for major psychoses symptomatology.

Adult↗
PubMed2001

No association between dopamine D(2) and D(4) receptor gene variants and antidepressant activity of two selective serotonin reuptake inhibitors.

The possible association of the dopamine receptor D(2) (Ser 311Cys) and D(4) exon 3 (48 base pair repeat) gene variants with the antidepressant activity of selective serotonin reuptake inhibitors (SSRIs) was investigated in a sample of 364 inpatients affected by a major depressive episode treated with fluvoxamine, 300 mg/day (n=266), or paroxetine, 20-40 mg/day (n=98). The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression. Dopamine receptor D(2) (DRD2) and dopamine receptor D(4) (DRD4) allelic variants were determined in each subject by polymerase chain reaction. We observed that DRD2 and DRD4 variants were not associated with response to SSRI treatment. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, depressive symptoms at baseline, paroxetine and fluvoxamine plasma levels, and pindolol augmentation did not significantly influence the observed results. The investigated DRD2 and DRD4 gene variants therefore do not seem to play a major role in the antidepressant activity of SSRIs, at least in the present sample.

Major Depressive Disorder↗
PubMed2001

Tryptophan hydroxylase gene and major psychoses.

Disturbances of the serotoninergic neurotransmitter system have been implicated in the pathogenesis of mood disorders. The tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, has been recently reported to be associated with bipolar disorder. In this study, we investigated TPH A218C gene variants in a sample of subjects affected by major psychoses. One thousand four hundred and twenty-four inpatients affected by bipolar (n=627), major depressive (n=511), schizophrenic (n=210), delusional (n=48) disorder and psychotic disorder not otherwise specified (n=27) (DSM-IV) were included; all patients and 380 controls were typed for the TPH variants using PCR techniques. A sub-sample of 963 patients was assessed using the Operational Criteria for Psychotic Illness (OPCRIT). TPH variants were not associated with major psychoses, but a trend was observed toward an excess of TPH*A/A in bipolar disorder. The analysis of symptomatology factors did not show any significant difference either; however, a trend was observed for males with the TPH*A genotype to have lower depressive symptoms compared with TPH*C subjects. Possible stratification factors such as current age and age of onset did not affect the observed results. TPH A218C variants are not, therefore, a major liability factor for the symptoms of major psychoses to have in the present sample. TPH*A containing variants may be a protective factor for depressive symptoms among male subjects with mood disorders or for a subtype of mood disorders characterized by a mainly manic form of symptomatology.

Adult↗
PubMed2001

DRD4 exon 3 variants associated with delusional symptomatology in major psychoses: a study on 2,011 affected subjects.

We previously reported an association of DRD4 exon3 long allele variants with delusional symptomatology independently from diagnoses. The aim of this investigation was to study DRD4 in major psychoses and to test the association in a larger sample. We studied 2,011 inpatients affected by bipolar disorder (n = 811), major depressive disorder (n = 635), schizophrenia (n = 419), delusional disorder (n = 104), psychotic disorder not otherwise specified (n = 42), and 601 healthy controls. A subsample of 1,264 patients were evaluated using the OPCRIT checklist and differences of symptomatology factor scores among genetic variants were assessed using one-way analysis of variance (ANOVA). DRD4 allele and genotype frequencies in bipolars, schizophrenics, delusionals, and psychotic NOS were not significantly different from controls; major depressives showed a trend toward an excess of DRD4*Short and DRD4*Short/Short variants versus controls. The ANOVA on factor scores in the whole subsample of 1,264 subjects showed a significant difference on delusion factor in allele analysis (P = 0.007), and in genotype one (P = 0.018), with DRD4*Long containing variants associated with severe symptomatology. The analysis in the replication subjects only (n = 803) showed a trend in the same direction, though not reaching the significance level. This analysis in an enlarged sample suggests that DRD4*Long alleles exert a small but significant influence on the delusional symptomatology in subjects affected by major psychoses.

Adult↗
PubMed2001

Temporal envelope expansion of speech in noise for normal-hearing and hearing-impaired listeners: effects on identification performance and response times.

The effects of expanding the temporal envelope of speech sounds on speech identification in noise were investigated in normal-hearing and hearing-impaired listeners. Expansion was performed by applying a power-law transformation to the low-frequency temporal modulations (<500 Hz) of vowel-consonant-vowel logatomes presented against a background noise. Stimuli were spectrally degraded, allowing a direct examination of the perceptual effects induced by the modification of the temporal envelope alone on speech reception. This study extended a previous study conducted by Lorenzi et al. [1999. Hear. Res. 136, 131--138] by measuring the effects of envelope expansion on both identification performance and response times in normal-hearing and hearing-impaired listeners. Overall, the results show that temporal expansion yields only small improvements in identification scores (approximately 5%) in normal-hearing listeners. No effect of expansion on identification scores was observed in hearing-impaired listeners. On the other hand, the results show that expansion led to a significant decrease in response times in both normal-hearing and hearing-impaired listeners. The average benefit from expansion was about 65 ms in both groups. These results suggest that expanding the temporal envelope of speech sounds presented in noise may improve 'ease of listening' in both normal-hearing and hearing-impaired listeners.

Adult↗
PubMed2001

Tryptophan hydroxylase gene associated with paroxetine antidepressant activity.

The possible association of the A218C tryptophan hydroxylase (TPH) gene variant with the antidepressant activity of paroxetine was investigated in a sample of 121 inpatients affected by a major depressive episode and treated with paroxetine 20-40 mg with either placebo or pindolol in a double blind design for 4 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. TPH allelic variants were determined in each subject using a PCR-based technique. TPH*A/A and TPH*A/C variants were associated with a poorer response to paroxetine treatment when compared to TPH*C/C (P=0.005); this difference was not present in the pindolol augmented group. Other variables, such as sex, diagnosis, presence of psychotic features, severity of depressive symptomatology at baseline and paroxetine plasma level, were not associated with the outcome. TPH gene variants are therefore a possible modulator of paroxetine antidepressant activity.

Antidepressive Agents, Second-Generation↗
PubMed2001

Measurement of first- and second-order modulation detection thresholds in listeners with cochlear hearing loss.

First- and second-order modulation detection thresholds were measured in normal hearing and hearing-impaired listeners. 'First-order' modulation detection thresholds correspond to the ability of listeners to detect sinusoidal amplitude modulation (SAM); they are measured as a function of the frequency of that modulation, f(m). 'Second-order' modulation detection thresholds correspond to the ability to detect sinusoidal modulation applied to the modulation depth of a SAM signal; they are measured as a function of the frequency of the modulation applied to the modulation depth (referred to as f(m)'). In this case, the SAM signal acts as a 'carrier' stimulus of frequency f(m) and sinusoidal modulation of the SAM-signal's modulation depth (at rate f(m)') generates two additional components in the modulation spectrum at f(m)-f(m)' and f(m)+f(m)'. In both groups of listeners, first-order modulation detection thresholds were measured for modulation frequencies f(m) ranging between 4 Hz and 32 Hz, and second-order modulation detection thresholds were measured for second-order modulation frequencies f(m)' ranging between 1 Hz and 11 Hz, using a fixed first-order modulation frequency f(m) of 16 Hz. The results showed that, in hearing-impaired listeners: first-order modulation detection thresholds were within the normal range up to f(m) = 16 Hz and poorer than normal at f(m) = 32 Hz; second-order modulation detection thresholds were within the normal range at f(m)' = 3, 5 and 11 Hz, and poorer than normal at f(m)' = 1 Hz and 7 Hz. These results suggest that cochlear damage has little effect on the detection of both sinusoidal and complex temporal envelopes.

Adult↗
PubMed2001

Second-order temporal modulation transfer functions.

Detection thresholds were measured for a sinusoidal modulation applied to the modulation depth of a sinusoidally amplitude-modulated (SAM) white noise carrier as a function of the frequency of the modulation applied to the modulation depth (referred to as f'm). The SAM noise acted therefore as a "carrier" stimulus of frequency fm, and sinusoidal modulation of the SAM-noise modulation depth generated two additional components in the modulation spectrum: fm-f'm and fm+f'm. The tracking variable was the modulation depth of the sinusoidal variation applied to the "carrier" modulation depth. The resulting "second-order" temporal modulation transfer functions (TMTFs) measured on four listeners for "carrier" modulation frequencies fm of 16, 64, and 256 Hz display a low-pass segment followed by a plateau. This indicates that sensitivity to fluctuations in the strength of amplitude modulation is best for fluctuation rates f'm below about 2-4 Hz when using broadband noise carriers. Measurements of masked modulation detection thresholds for the lower and upper modulation sideband suggest that this capacity is possibly related to the detection of a beat in the sound's temporal envelope. The results appear qualitatively consistent with the predictions of an envelope detector model consisting of a low-pass filtering stage followed by a decision stage. Unlike listeners' performance, a modulation filterbank model using Q values > or = 2 should predict that second-order modulation detection thresholds should decrease at high values of f'm due to the spectral resolution of the modulation sidebands (in the modulation domain). This suggests that, if such modulation filters do exist, their selectivity is poor. In the latter case, the Q value of modulation filters would have to be less than 2. This estimate of modulation filter selectivity is consistent with the results of a previous study using a modulation-masking paradigm [S. D. Ewert and T. Dau, J. Acoust. Soc. Am. 108, 1181-1196 (2000)].

Adult↗
PubMed2001

Second-order modulation detection thresholds for pure-tone and narrow-band noise carriers.

Modulation perception has typically been characterized by measuring detection thresholds for sinusoidally amplitude-modulated (SAM) signals. This study uses multicomponent modulations. "Second-order" temporal modulation transfer functions (TMTFs) measure detection thresholds for a sinusoidal modulation of the modulation waveform of a SAM signal [Lorenzi et al., J. Acoust. Soc. Am. 110, 1030-2038 (2001)]. The SAM signal therefore acts as a "carrier" stimulus of frequency fm, and sinusoidal modulation of the SAM signal's modulation depth (at rate f'm) generates two additional components in the modulation spectrum at fm - f'm and fm + f'm. There is no spectral energy at the envelope beat frequency f'm in the modulation spectrum of the "physical" stimulus. In the present study, second-order TMTFs were measured for three listeners when fm was 16, 64, and 256 Hz. The carrier was either a 5-kHz pure tone or a narrow-band noise with center frequency and bandwidth of 5 kHz and 2 Hz, respectively. The narrow-band noise carrier was used to prevent listeners from detecting spectral energy at the beat frequency f'm in the "internal" stimuli's modulation spectrum. The results show that, for the 5-kHz pure-tone carrier, second-order TMTFs are nearly low pass in shape; the overall sensitivity and cutoff frequency measured on these second-order TMTFs increase when fm increases from 16 to 256 Hz. For the 2-Hz-wide narrow-band noise carrier, second-order TMTFs are nearly flat in shape for fm = 16 and 64 Hz, and they show a high-pass segment for fm = 256 Hz. These results suggest that detection of spectral energy at the envelope beat frequency contributes in part to the detection of second-order modulation. This is consistent with the idea that nonlinear mechanisms in the auditory pathway produce an audible distortion component at the envelope beat frequency in the internal modulation spectrum of the sounds.

Adult↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗