Sleep abnormalities in individuals at clinical high risk for psychosis.

Youth at clinical high risk (CHR) represent a unique population enriched for precursors of major psychiatric disorders. Sleep disturbances are consistently reported in CHR individuals. However, there is a dearth of studies investigating quantifiable objective measures of sleep dysfunction in CHR youth. In this study, sleep high density (hd)-EEG recordings were collected in twenty-two CHR and twenty healthy control (HC) subjects. Sleep architecture parameters, as well as sleep EEG power spectra in five frequency bands, were computed and compared between CHR and HC groups during non-rapid eye movement (NREM) sleep. Furthermore, correlation analyses between sleep EEG power spectra, sleep architecture parameters, and clinical symptoms, assessed with the scale of prodromal symptoms (SOPS), were conducted in CHR participants. Our results show that CHR individuals had more wakefulness after sleep onset (WASO) compared to HC participants. CHR also showed a higher NREM sleep gamma EEG power, which was observed in a large fronto-parieto-occipital area, relative to HC. Additionally, higher NREM gamma activity in lateral fronto-occipital regions was associated with more WASO, and increased NREM gamma power in medial fronto/parietal areas correlated with worse SOPS negative symptoms. Altogether, these findings suggest that topographically specific increases in EEG gamma activity during NREM sleep represent neurophysiological signatures underlying some of the objectively assessed sleep disturbances and clinical symptoms of CHR individuals.

Sleep disturbances in schizophrenia: what we know, what still needs to be done.

Sleep disturbances are commonly observed in schizophrenia (SCZ) and are associated with worse psychotic symptoms and poorer clinical outcomes. Early polysomnography studies have focused on characterizing differences in sleep architecture between patients with SCZ and healthy controls. More recently, research has focused on sleep-specific EEG oscillations, such as sleep spindles and slow waves, which reflect the integrity of underlying thalamo-cortical networks. Furthermore, high-density (hd)-EEG (≥64 channels), which affords enhanced spatial resolution, has been employed to better localize abnormalities in sleep characteristics and related thalamo-cortical circuits in patients with SCZ and related disorders. In this article, we will review the most relevant sleep abnormalities reported in SCZ, with an emphasis on recent findings, and propose directions for future research.

Topographic deficits in sleep spindle density and duration point to frontal thalamo-cortical dysfunctions in first-episode psychosis.

Sleep spindles are NREM sleep EEG oscillations, which are initiated within the thalamus and are regulated by thalamo-cortical circuits. Previous work from our and other research groups has shown marked spindle deficits in patients with schizophrenia (SCZ). However, the presence of spindle impairments at illness onset, including which parameters are most affected, their topographic characteristics, and their relationships with clinical symptoms have yet to be characterized. In this study we performed sleep high density (hd)-EEG recordings in twenty-seven first-episode psychosis (FEP) patients and twenty-three healthy controls (HC). Several spindle parameters-amplitude, duration, and density-were calculated and compared across groups. FEP patients showed reduced spindle duration and density, but not in spindle amplitude relative to HC. These spindles reductions were localized in a frontal area and predicted the severity of FEP patients' negative symptoms. Altogether, these findings indicate that spindle deficits are present at the beginning of psychosis, contribute to clinical symptomatology, and point to frontal thalamo-cortical dysfunctions, thus providing a potential treatment target for early interventions in SCZ and related psychotic disorders.

Abnormalities in the evoked frontal oscillatory activity of first-episode psychosis: A TMS/EEG study.

TMS with simultaneous EEG allows assessing the intrinsic oscillatory activity of cortical neurons. We recently showed reduced frontal cortical oscillations in chronic schizophrenia (SCZ). Here we investigated the oscillatory activity of first-episode psychosis (FEP) patients after TMS of a frontal area, the motor cortex. Compared to healthy controls, FEP patients had significantly reduced beta/low gamma oscillations, which were associated to worse clinical symptoms. Altogether, this study demonstrates that TMS/EEG recordings: 1) are feasible in acute, early-course psychotic patients; and 2) reveal intrinsic oscillatory deficits at illness onset, which may help design more effective, early interventions in SCZ.

Reduced frontal slow wave density during sleep in first-episode psychosis.

BACKGROUND: Sleep disturbances are commonly reported in psychotic patients and often contribute to the manifestation and severity of their symptoms. Slow waves characterize the deepest stage of NREM sleep, and their occurrence is critical for restorative sleep. Slow wave abnormalities have been reported in patient with schizophrenia, especially when experiencing an exacerbation of psychosis. However, their presence and delineation, with an emphasis on topography, in first-episode psychosis patients (FEP) have not yet been characterized. METHODS: We performed sleep high density (hd)-EEG recordings in twenty FEP patients and twenty healthy control subjects (HC). Slow wave activity (SWA) and several other slow wave parameters, e.g. density, amplitude, up- and down-slopes, were calculated at each electrode location and compared across groups. Additionally, the association between slow wave characteristics and clinical symptoms was assessed. RESULTS: FEP patients showed a reduction selectively in slow-wave density relative to HC, and this reduction was significant in a large frontal area, including channels overlying the prefrontal cortex. Furthermore, slow wave density was inversely correlated with the severity of FEP positive symptoms. CONCLUSIONS: Abnormalities in slow waves are present at the beginning of psychosis, occur in frontal-prefrontal regions that are highly dysfunctional in psychotic patients, and are associated with their positive symptom severity. Building on these findings, future work will help establish the direction of these associations (i.e., if clinical symptoms precede, coincide, or follow SW deficits), which will determine whether ameliorating slow wave sleep deficits is a viable treatment target in early psychosis.

Investigating the neurobiology of schizophrenia and other major psychiatric disorders with Transcranial Magnetic Stimulation.

Characterizing the neurobiology of schizophrenia and other major psychiatric disorders is one of the main challenges of the current research in psychiatry. The availability of Transcranial Magnetic Stimulation (TMS) allows to directly probe virtually any cortical areas, thus providing a unique way to assess the neurophysiological properties of cortical neurons. This article presents a review of studies employing TMS in combination with Motor Evoked Potentials (TMS/MEPs) and high density Electroencephalogram (TMS/hd-EEG) in schizophrenia and other major psychiatric disorders. Studies were identified by conducting a PubMed search using the following search item: "transcranial magnetic stimulation and (Schizophrenia or OCD or MDD or ADHD)". Studies that utilized TMS/MEP and/or TMS/hd-EEG measures to characterize cortical excitability, inhibition, oscillatory activity, and/or connectivity in psychiatric patients were selected. Across disorders, patients displayed a pattern of reduced cortical inhibition, and to a lesser extent increased excitability, in the motor cortex, which was most consistently established in Schizophrenia. Furthermore, psychiatric patients showed abnormalities in a number of TMS-evoked EEG oscillations, which was most prominent in the prefrontal cortex of Schizophrenia relative to healthy comparison subjects. Overall, results from this review point to significant impairments in cortical excitability, inhibition, and oscillatory activity, especially in frontal areas, in several major psychiatric disorders. Building on these findings, future studies employing TMS-based experimental paradigms may help elucidating the neurobiology of these psychiatric disorders, and may assess the contribution of TMS-related measures in monitoring and possibly maximizing the effectiveness of treatment interventions in psychiatric populations.

Schizophrenia and sleep disorders: links, risks, and management challenges.

Schizophrenia is a major psychiatric disorder that has a massive, long-lasting negative impact on the patients as well as society. While positive symptoms (i.e., delusions and hallucinations), negative symptoms (i.e., anhedonia, social withdrawal), and cognitive impairments are traditionally considered the most prominent features of this disorder, the role of sleep and sleep disturbances has gained increasing prominence in clinical practice. Indeed, the vast majority of patients with schizophrenia report sleep abnormalities, which tend to precede illness onset and can predict an acute exacerbation of psychotic symptoms. Furthermore, schizophrenia patients often have a comorbid sleep disorder, including insomnia, obstructive sleep apnea, restless leg syndrome, or periodic limb movement disorder. Despite accumulating data, the links between sleep disorders and schizophrenia have not been thoroughly examined, in part because they are difficult to disentangle, as numerous factors contribute to their comorbidity, including medication status. Additionally, sleep disorders are often not the primary focus of clinicians treating this population, despite studies suggesting that comorbid sleep disorders carry their own unique risks, including worsening of psychotic symptoms and poorer quality of life. There is also limited information about effective management strategies for schizophrenia patients affected by significant sleep disturbances and/or sleep disorders. To begin addressing these issues, the present review will systematically examine the literature on sleep disorders and schizophrenia, focusing on studies related to 1) links between distinct sleep disorders and schizophrenia; 2) risks unique to patients with a comorbid sleep disorder; and 3) and management challenges and strategies.