Examining long-acting injectable antipsychotic (depot) medication in the elderly: a five-year retrospective cross-sectional study evaluating depot use in an Australian psychogeriatric service.

OBJECTIVE: The primary aim was to examine the use of long-acting injectable (LAI) antipsychotic (depot) medication in a cohort of older patients in a community psychogeriatric service. METHOD: From 2014 to 2018, all patients who were on LAIs each year were analysed for various characteristics including their profile, type of LAI used, dose and relapse rates related to switching, ceasing and community treatment order (CTO) use. RESULTS: A total of 880 patients were managed by the service with 142 recorded cases of LAI use in total over the 5 years (16.1%). Second-generation antipsychotics (SGAs) outnumbered first-generation antipsychotics (FGAs) by 2:1, with a trend of increasing use of SGA LAIs. The most commonly used LAI was Paliperidone monthly injection (PP1M) (50.7%). Lower than usual adult chlorpromazine equivalent daily doses of LAIs were used. The relapse rate while on a LAI was 13.4%. Moreover, 54.9% of the patients on LAIs were on a CTO. Relapse rates were lower on LAIs in combination with a CTO (7.7%). CONCLUSIONS: LAIs, especially the SGAs, are increasingly used in our service. In combination with a CTO, LAIs are an effective treatment in reducing relapse rates in the elderly.

Brief monocular deprivation as an assay of short-term visual sensory plasticity in schizophrenia - "the binocular effect".

BACKGROUND: Visual sensory processing deficits are consistently observed in schizophrenia, with clear amplitude reduction of the visual evoked potential (VEP) during the initial 50-150 ms of processing. Similar deficits are seen in unaffected first-degree relatives and drug-naïve first-episode patients, pointing to these deficits as potential endophenotypic markers. Schizophrenia is also associated with deficits in neural plasticity, implicating dysfunction of both glutamatergic and GABAergic systems. Here, we sought to understand the intersection of these two domains, asking whether short-term plasticity during early visual processing is specifically affected in schizophrenia. METHODS: Brief periods of monocular deprivation (MD) induce relatively rapid changes in the amplitude of the early VEP - i.e., short-term plasticity. Twenty patients and 20 non-psychiatric controls participated. VEPs were recorded during binocular viewing, and were compared to the sum of VEP responses during brief monocular viewing periods (i.e., Left-eye + Right-eye viewing). RESULTS: Under monocular conditions, neurotypical controls exhibited an effect that patients failed to demonstrate. That is, the amplitude of the summed monocular VEPs was robustly greater than the amplitude elicited binocularly during the initial sensory processing period. In patients, this "binocular effect" was absent. LIMITATIONS: Patients were all medicated. Ideally, this study would also include first-episode unmedicated patients. CONCLUSION: These results suggest that short-term compensatory mechanisms that allow healthy individuals to generate robust VEPs in the context of MD are not effectively activated in patients with schizophrenia. This simple assay may provide a useful biomarker of short-term plasticity in the psychotic disorders and a target endophenotype for therapeutic interventions.

The N1 auditory evoked potential component as an endophenotype for schizophrenia: high-density electrical mapping in clinically unaffected first-degree relatives, first-episode, and chronic schizophrenia patients.

The N1 component of the auditory evoked potential (AEP) is a robust and easily recorded metric of auditory sensory-perceptual processing. In patients with schizophrenia, a diminution in the amplitude of this component is a near-ubiquitous finding. A pair of recent studies has also shown this N1 deficit in first-degree relatives of schizophrenia probands, suggesting that the deficit may be linked to the underlying genetic risk of the disease rather than to the disease state itself. However, in both these studies, a significant proportion of the relatives had other psychiatric conditions. As such, although the N1 deficit represents an intriguing candidate endophenotype for schizophrenia, it remains to be shown whether it is present in a group of clinically unaffected first-degree relatives. In addition to testing first-degree relatives, we also sought to replicate the N1 deficit in a group of first-episode patients and in a group of chronic schizophrenia probands. Subject groups consisted of 35 patients with schizophrenia, 30 unaffected first-degree relatives, 13 first-episode patients, and 22 healthy controls. Subjects sat in a dimly lit room and listened to a series of simple 1,000-Hz tones, indicating with a button press whenever they heard a deviant tone (1,500 Hz; 17% probability), while the AEP was recorded from 72 scalp electrodes. Both chronic and first-episode patients showed clear N1 amplitude decrements relative to healthy control subjects. Crucially, unaffected first-degree relatives also showed a clear N1 deficit. This study provides further support for the proposal that the auditory N1 deficit in schizophrenia is linked to the underlying genetic risk of developing this disorder. In light of recent studies, these results point to the N1 deficit as an endophenotypic marker for schizophrenia. The potential future utility of this metric as one element of a multivariate endophenotype is discussed.

Acoustic and temporal analysis of speech: A potential biomarker for schizophrenia.

Currently, there are no established objective biomarkers for the diagnosis or monitoring of schizophrenia. It has been previously reported that there are notable qualitative differences in the speech of schizophrenics. The objective of this study was to determine whether a quantitative acoustic and temporal analysis of speech may be a potential biomarker for schizophrenia. In this study, 39 schizophrenic patients and 18 controls were digitally recorded reading aloud an emotionally neutral text passage from a children's story. Temporal, energy and vocal pitch features were automatically extracted from the recordings. A classifier based on linear discriminant analysis was employed to differentiate between controls and schizophrenic subjects. Processing the recordings with the algorithm developed demonstrated that it is possible to differentiate schizophrenic patients and controls with a classification accuracy of 79.4% (specificity=83.6%, sensitivity=75.2%) based on speech pause related parameters extracted from recordings carried out in standard office (non-studio) environments. Acoustic and temporal analysis of speech may represent a potential tool for the objective analysis in schizophrenia.

Visual sensory processing deficits in patients with bipolar disorder revealed through high-density electrical mapping.

BACKGROUND: Etiological commonalities are apparent between bipolar disorder and schizophrenia. For example, it is becoming clear that both populations show similar electrophysiological deficits in the auditory domain. Recent studies have also shown robust visual sensory processing deficits in patients with schizophrenia using the event-related potential technique, but this has not been formally tested in those with bipolar disorder. Our goal here was to assess whether early visual sensory processing in patients with bipolar disorder, as indexed by decreased amplitude of the P1 component of the visual evoked potential (VEP), would show a similar deficit to that seen in those with schizophrenia. Since the P1 deficit has already been established as an endophenotype in schizophrenia, a finding of commonality between disorders would raise the possibility that it represents a measure of common genetic liability. METHODS: We visually presented isolated-check stimuli to euthymic patients with a diagnosis of bipolar disorder and age-matched healthy controls within a simple go/no-go task and recorded VEPs using high-density (72-channel) electroencephalography. RESULTS: The P1 VEP amplitude was substantially reduced in patients with bipolar disorder, with an effect size of f = 0.56 (large according to Cohen's criteria). LIMITATIONS: Our sample size was relatively small and as such, did not allow for an examination of potential relations between the physiologic measures and clinical measures. CONCLUSION: This reduction in P1 amplitude among patients with bipolar disorder represents a dysfunction in early visual processing that is highly similar to that found repeatedly in patients with schizophrenia and their healthy first-degree relatives. Since the P1 deficit has been related to susceptibility genes for schizophrenia, our results raise the possibility that the deficit may in fact be more broadly related to the development of psychosis and that it merits further investigation as a candidate endophenotype for bipolar disorder.

Visual sensory processing deficits in Schizophrenia and their relationship to disease state.

CONTEXT: Visual Evoked Potential (VEP) abnormalities have been a fairly consistent finding in patients with schizophrenia, and it has been suggested that electrophysiological markers of early sensory processing may be useful as trait markers for the illness, and for development as potential diagnostic measures. OBJECTIVE: Clear amplitude reductions in the occipital P1 component of the VEP (approximately 100 ms), have been repeatedly demonstrated in patients with schizophrenia. Here, we investigated whether the extent of this deficit was related to age, clinical symptoms, medication status and length of illness, in a large cohort of ethnically homogenous patients. DESIGN, SETTING AND PARTICIPANTS: VEP responses to simple isolated-check stimuli were examined in 52 DSM-IV diagnosed patients with schizophrenia, and compared with responses from 26 healthy age-matched control subjects. Using high-density electrical scalp recordings, we assessed the integrity of the visual P1 component across the two groups. This study was conducted at St.Vincent's Psychiatric Hospital in Fairview, Dublin, Ireland. RESULTS: Substantially reduced P1 amplitude was demonstrated in the patient group compared to controls. The deficit was not linked to age, length of illness or medication status. A small positive correlation, accounting for about 11% of the variance, was found between P1 amplitude and clinical symptoms scales (BPRS and SANS). In addition, we found that a slightly later (~110 ms) fronto-central component was relatively increased in the patient group, and was inversely correlated with the occipital P1 amplitude in the patients, but not in the healthy control subjects. CONCLUSIONS: Our findings clearly demonstrate a deficit in early visual processing in patients with schizophrenia (with a large effect size; Cohen's d = 0.7) that is unrelated to chronicity. The results are consistent with recent findings showing that the P1 deficit is endophenotypic of the disorder and related to genetic risk factors rather than the disease process itself.

Are auditory-evoked frequency and duration mismatch negativity deficits endophenotypic for schizophrenia? High-density electrical mapping in clinically unaffected first-degree relatives and first-episode and chronic schizophrenia.

BACKGROUND: Mismatch negativity (MMN) is a negative-going event-related potential (ERP) component that occurs in response to intermittent changes in constant auditory backgrounds. A consistent finding across a large number of studies has been impaired MMN generation in schizophrenia, which has been interpreted as evidence for fundamental deficits in automatic auditory sensory processing. The aim of this study was to investigate the extent to which dysfunction in MMN generation might represent an endophenotypic marker for schizophrenia. METHODS: We measured MMN to deviants in duration (25 msec, 1000 Hz) and deviants in pitch (50 msec, 1200 Hz) relative to standard tones (50 msec, 1000 Hz) in 45 chronic schizophrenia patients, 25 of their first-degree unaffected biological relatives, 12 first-episode patients, and 27 healthy control subjects. RESULTS: In line with previous work, MMN amplitudes to duration deviants (but not to pitch deviants) were significantly reduced in patients with chronic schizophrenia compared with control subjects. However, both duration and pitch MMNs were completely unaffected in the first-degree biological relatives and this was also the case for the first-episode patients. Furthermore, length of illness did not predict the extent of MMN deficit. CONCLUSIONS: These findings suggest that the MMN deficit seen in schizophrenia patients is most likely a consequence of the disease and that MMN, at least to basic auditory feature deviants, is at best only weakly endophenotypic for schizophrenia.

Dissecting the cellular contributions to early visual sensory processing deficits in schizophrenia using the VESPA evoked response.

Electrophysiological research has shown clear dysfunction of early visual processing mechanisms in patients with schizophrenia. In particular, the P1 component of the visual evoked potential (VEP) is substantially reduced in amplitude in patients. A novel visual evoked response known as the VESPA (Visual Evoked Spread Spectrum Analysis) was recently described. This response has a notably different scalp topography from that of the traditional VEP, suggesting preferential activation of a distinct subpopulation of cells. As such, this method constitutes a potentially useful candidate for investigating cellular contributions to early visual processing deficits. In this paper we compare the VEP and VESPA responses between a group of healthy control subjects and a group of schizophrenia patients. We also introduce an extension of the VESPA method to incorporate nonlinear processing in the visual system. A significantly reduced P1 component was found in patients using the VEP (with a large effect size; Cohen's d=1.6), while there was no difference whatsoever in amplitude between groups for either the linear or nonlinear VESPA. This pattern of results points to a highly specific cellular substrate of early visual processing deficits in schizophrenia, suggesting that these deficits are based on dysfunction of magnocellular pathways with parvocellular processing remaining largely intact.

Early visual sensory deficits as endophenotypes for schizophrenia: high-density electrical mapping in clinically unaffected first-degree relatives.

CONTEXT: The imperative to establish so-called endophenotypes-quantifiable measures of risk for neurological dysfunction-is a growing focus of research in schizophrenia. Electrophysiological markers of sensory processing, observable in human event-related potentials, hold great promise in this regard, lying closer to underlying physiology than descriptive clinical diagnostic tests. OBJECTIVE: Early visual processing deficits, as measured by clear amplitude reductions in the occipital P1 component of the visual event-related potential, have been repeatedly demonstrated in patients with schizophrenia. However, before P1 amplitude may be considered as an endophenotypic marker for schizophrenia, it is necessary to establish its sensitivity to genetic liability. DESIGN, SETTING, AND PARTICIPANTS: Event-related potential responses to simple visual isolated-check stimuli were examined in 25 clinically unaffected first-degree relatives of patients with schizophrenia and 15 DSM-IV-diagnosed schizophrenia probands and compared with responses from 26 healthy, age-matched control subjects. Using high-density electrical scalp recordings, between-groups analysis assessed the integrity of the visual P1 component across the 3 groups. The study was conducted at St Vincent's Psychiatric Hospital in Fairview, Dublin, Ireland. RESULTS: Substantially reduced P1 amplitude was demonstrated in both relatives and probands compared with controls with topographical mapping and inverse source analysis localizing this deficit largely to midline regions in early visual sensory cortices and regions of the dorsal visual stream. Additional later differences between these groups, where the relatives actually show larger amplitude responses, may point toward compensatory mechanisms at play in relatives. CONCLUSIONS: Our findings demonstrate a deficit in early visual processing in clinically unaffected first-degree relatives of patients with schizophrenia, providing evidence that this deficit may serve as a genetic marker for this disorder. The efficacy of using P1 amplitude as an endophenotype is underscored by the observation of a large effect size (d=0.9) over scalp sites where the deficit was maximal.