Neurobiological support to the diagnosis of ADHD in stimulant-naïve adults: pattern recognition analyses of MRI data.

OBJECTIVE: In adulthood, the diagnosis of attention-deficit/hyperactivity disorder (ADHD) has been subject of recent controversy. We searched for a neuroanatomical signature associated with ADHD spectrum symptoms in adults by applying, for the first time, machine learning-based pattern classification methods to structural MRI and diffusion tensor imaging (DTI) data obtained from stimulant-naïve adults with childhood-onset ADHD and healthy controls (HC). METHOD: Sixty-seven ADHD patients and 66 HC underwent high-resolution T1-weighted and DTI acquisitions. A support vector machine (SVM) classifier with a non-linear kernel was applied on multimodal image features extracted on regions of interest placed across the whole brain. RESULTS: The discrimination between a mixed-gender ADHD subgroup and individually matched HC (n = 58 each) yielded area-under-the-curve (AUC) and diagnostic accuracy (DA) values of up to 0.71% and 66% (P = 0.003) respectively. AUC and DA values increased to 0.74% and 74% (P = 0.0001) when analyses were restricted to males (52 ADHD vs. 44 HC). CONCLUSION: Although not at the level of clinically definitive DA, the neuroanatomical signature identified herein may provide additional, objective information that could influence treatment decisions in adults with ADHD spectrum symptoms.

Temporal stability of auditory evoked potentials at different stimulation rates.

1. We determined the temporal stability of the N1 and P2 waves of the auditory evoked potentials (AEP) for twelve healthy subjects who were tested in two sessions separated by 2 to 63 days (mean = 25 days). AEP were obtained at two different stimulation rates (1/s and 0.3/s). In addition to wave amplitude and latency, the latency difference and the amplitude ratio between the two stimulation rates were calculated. 2. Mean amplitudes, latencies, latency differences and amplitude ratios were not significantly different between the two sessions. Pearson's correlation was significant only for N1 latency at the 1/s stimulation rate (r = 0.64, P = 0.02). 3. Factors such as arousal and other subjective states of the subjects, personality traits, as well as technical aspects of the examinations, may have influenced the temporal stability of the AEP.

Changes in P300 latency and amplitude in schizophrenic patients and healthy controls during the examination.

In 30 schizophrenic patients (sixteen of the paranoid subtype, 14 of the nonparanoid) and healthy controls (n = 30) event-related potentials were obtained with a somatosensory reaction-time (RT) version of the "oddball paradigm" by stimulating the right (first run) and the left (second run) median nerve. Variations of P300 amplitude and latency and of RT within the average (30 trials) were studied by fractionating off-line the original averages in three subaverages. After stimulation of the right median nerve oscillations on P300 amplitude and latency were observed. After stimulation of the left median nerve there was a trend toward a decrease of the P300 amplitude that reached significance at the electrode P3 for patients (p = 0.014) and at the electrode P4 for controls (p = 0.025). The P300 latency showed variations for patients and controls. The mean-RT was prolonged across the subaverages only for schizophrenics, reaching significance after stimulation of the right median nerve. Paranoid and nonparanoid schizophrenic patients showed similar results on P300 and RT parameters across the subaverages. These results are discussed in terms of the influence of motivation and task involvement on the P300 amplitude. These could be unspecific factors that account for the habituation of the P300 along the examination.

Functional relationship between brain regions in schizophrenia evaluated with Pearson's correlation between event-related potentials.

As part of a study of the somatosensory P300 event-related potential (ERP) in paranoid and nonparanoid schizophrenic patients (8) Pearson's product-moment correlations between ERP waveforms were calculated to study the functional relationship between brain areas. ERP were recorded from F3, F4, P3 and P4; interhemispheric (F3 to F4; P3 to P4) and intrahemispheric (F3 to P3; F4 to P4) correlations were obtained. There was no significant difference among the paranoid and nonparanoid patients and healthy controls for both the interhemispheric and the intrahemispheric correlations. The lack of disruption of functional relationship between brain areas on the patients do not support the hypofrontality and the laterality hypothesis of schizophrenia. However, the use of neuroleptics by the patients, the study of the whole waveforms and not parts of them and the use of linked-ears reference could account for these negative results.

Differences between paranoid and nonparanoid schizophrenic patients on the somatosensory P300 event-related potential.

Event-related potentials were recorded from schizophrenic patients (n = 30) and healthy controls (n = 30) using a somatosensory-reaction-time version of the oddball paradigm, by stimulating the right and the left median nerve. Latency, amplitude, duration and area of the P300 were measured. The patient group was subdivided into a paranoid (n = 16) and a nonparanoid (n = 14) subgroup and each was compared to controls. After stimulation of the right median nerve the nonparanoid group had a significantly prolonged P300 latency and a normal amplitude. The paranoid subgroup had a trend toward reduction of the P300 amplitude; its P300 latency was normal. After stimulation of the left median nerve, a prolongation of the P300 latency was observed in the paranoid subgroup. This subgroup had also a reduced P300 amplitude, while the nonparanoid patients had both values comparable to those of the controls. Duration and area were not significantly different between the two subgroups of patients and controls. Paranoid and nonparanoid patients showed a different behavior on reaction time parameters. No relationship was observed between P300 parameters and clinical ratings, neuroleptic dose and demographic data. The P300 parameters did not correlate with the reaction time measures. These results are discussed in terms of a disturbance of CNS inhibitory mechanisms in cognitive processes of paranoid schizophrenic patients and could be a further indication that different subtypes of schizophrenia may have different biological substrates.

Higher morbidity risk for schizophrenia in males: fact or fiction?

Male to female ratios in published annual incidence rates for schizophrenia range from 0.70 to 3.47. These variations between studies are attributed to differences in sampling, diagnostic criteria, design characteristics, and methods of calculation, which limit the quality of the studies. In an effort to overcome these shortcomings, we collected a comprehensive sample of 392 consecutive first admissions with a diagnosis of schizophrenia or a similar disorder out of a population of 1.5 million in a central region of western Germany. In this large representative sample, no significant gender differences in the incidence of schizophrenia could be detected regardless of different diagnostic definitions.

Temporal stability of auditory evoked potentials at different stimulation rates

1. We determined the temporal stability of the N1 and P2 waves of the auditory evoked potentials (AEP) for twelve healthy subjects who were tested in two sessions separated by 2 to 63 days (mean = 25 days). AEP were obtained at two different stimulation rates (1/s and 0.3/s). In addition to wave amplitude and latency, the latency difference and the amplitude ratio between the two stimulation rates were calculated. 2. Mean amplitudes, latencies, latency differences and amplitude ratios were not significantly different between the two sessions. Pearson's correlation was significant only for N1 latency at the 1/s stimulation rate (r = 0.64, P = 0.02). 3. Factors such as arousal and other subjective states of the subjects, personality traits, as well as technical aspects of the examinations, may have influenced the temporal stability of the AEP