Armando D’Agostino

The dreaming brain/mind, consciousness and psychosis ☆

Several independent lines of research in neurobiology seem to support the phenomenologically-grounded view of the dreaming brain/mind as a useful model for psychosis. Hallucinatory phenomena and thought disorders found in psychosis share several peculiarities with dreaming, where internally generated, vivid sensorimotor imagery along with often heightened and incongruous emotion are paired with a decrease in ego functions which ultimately leads to a severe impairment in reality testing. Contemporary conceptualizations of severe mental disorders view psychosis as one psychopathological dimension that may be found across several diagnostic categories. Some experimental data have shown cognitive bizarreness to be equally elevated in dreams and in the waking cognition of acutely psychotic subjects and in patients treated with pro-dopaminergic drugs, independent of the underlying disorder. Further studies into the neurofunctional underpinnings of both conditions will help to clarify the use and validity of this model.

Stability of cognition across wakefulness and dreams in psychotic major depression

Cognitive bizarreness has been shown to be equally elevated in the dream and waking mentation of acutely symptomatic inpatients diagnosed with affective and non-affective psychoses. Although some studies have reported on dream content in non-psychotic depression, no study has previously measured this formal aspect of cognition in patients hospitalized for Psychotic Major Depression (PMD). Sixty-five dreams and 154 waking fantasy reports were collected from 11 PMD inpatients and 11 age- and sex-matched healthy controls. All narrative reports were scored by judges blind to diagnosis in terms of formal aspects of cognition (Bizarreness). Dream content was also scored (Hall/Van de Castle scoring system). Unlike controls, PMD patients had similar levels of cognitive bizarreness in their dream and waking mentation. Dreams of PMD patients also differed from those of controls in terms of content variables. In particular, Happiness, Apprehension and Dynamism were found to differ between the two groups. Whereas dream content reflects a sharp discontinuity with the depressive state, cognitive bizarreness adequately measures the stability of cognition across dreams and wakefulness in PMD inpatients.

Hypnagogic Hallucinations and Sleep Paralysis

Hypnagogic hallucinations and sleep paralysis are two associated features of narcolepsy that can also be found as isolated phenomena or within the context of other clinical conditions. Hypnagogic hallucinations are abnormal sensory perceptions experienced in the transition between wakefulness and sleep, whereas analogous hallucinations that occur upon awakening are called hypnopompic. Sleep paralysis is a transient paralysis of skeletal muscles associated with a clear waking mentation occurring in sleep/wake transitions. The two phenomena often occur together in narcoleptic subjects, provoking significant fear responses, especially when first experienced, because of the threatening and often terrifying content of the hallucinations and the impotence associated with the inability to move.

Non literal language comprehension in a large sample of first episode psychosis patients in adulthood

To date no data still exist on the comprehension of figurative language in the early phases of psychosis. The aim of this study is to investigate for the first time the comprehension of metaphors and idioms at the onset of the illness. Two-hundred-twenty eight (228) first episode psychosis (FEP) patients (168 NAP, non-affective psychosis; 60 AP, affective psychosis) and 70 healthy controls (HC) were assessed. Groups were contrasted on: a) type of stimulus (metaphors vs idioms) and b) type of response (OPEN = spontaneous explanations vs CLOSED = multiple choice answer). Moreover, a machine learning (ML) approach was adopted to classifying participants. Both NAP and AP had a poorer performance on OPEN metaphors and idioms compared to HC, with worse results on spontaneous interpretation of idioms than metaphors. No differences were observed between NAP and AP in CLOSED tasks. The ML approach points at CLOSED idioms as the best discriminating variable, more relevant than the set of pre-frontal and IQ scores. Deficits in non-figurative language may represent a core feature of psychosis. The possibility to identify linguistic features discriminating FEP may support the early recognition of patients at risk to develop psychosis, guiding provision of personalized and timely interventions.

Sleep endophenotypes of schizophrenia: slow waves and sleep spindles in unaffected first-degree relatives

Sleep spindles and slow waves are the main brain oscillations occurring in non-REM sleep. Several lines of evidence suggest that spindles are initiated within the thalamus, whereas slow waves are generated and modulated in the cortex. A decrease in sleep spindle activity has been described in Schizophrenia (SCZ), including chronic, early course, and early onset patients. In contrast, slow waves have been inconsistently found to be reduced in SCZ, possibly due to confounds like duration of illness and antipsychotic medication exposure. Nontheless, the implication of sleep spindles and slow waves in the neurobiology of SCZ and related disorders, including their heritability, remains largely unknown. Unaffected first-degree relatives (FDRs) share a similar genetic background and several neurophysiological and cognitive deficits with SCZ patients, and allow testing whether some of these measures are candidate endophenotypes. In this study, we performed sleep high-density EEG recordings to characterise the spatiotemporal features of sleep spindles and slow waves in FDRs of SCZ probands and healthy subjects (HS) with no family history of SCZ. We found a significant reduction of integrated spindle activity (ISAs) in FDRs relative to HS, whereas spindle density and spindle duration were not different between groups. FDRs also had decreased slow wave amplitude and slopes. Altogether, our results suggest that ISAs deficits might represent a candidate endophenotype for SCZ. Furthermore, given the slow wave deficits observed in FDRs, we propose that disrupted cortical synchronisation increases the risk for SCZ, but thalamic dysfunction is necessary for the disorder to fully develop.Diagnostics: Can sleep forewarn schizophrenia susceptibility?Sleep EEG recordings of schizophrenia patients’ relatives differ from healthy norms, suggesting a new hereditary biomarker of disease. Leading a collaboration of Italian and US scientists, the University of Milan’s Armando D’Agostino, Anna Castelnovo and Simone Sarasso compared the electrical activity of healthy subjects’ brains during sleep to that of first-degree relatives of schizophrenia patients. The team found a significant reduction in a parameter related to the amplitude of “sleep spindles,” one of the two major types of brainwaves in non-REM sleep, in the relatives’ brains. However, the density of sleep spindles—a schizophrenia-associated trait—was unaffected in relatives. The authors suggest that reduced sleep spindle amplitude may help to indicate an individual’s risk of developing schizophrenia. Other EEG features from relatives suggest a communication impairment between neuron groups, which may also predispose the illness.

A case of venlafaxine-induced kleptomania

Venlafaxine is usually categorized as a serotonin-norepinephrine reuptake inhibitor, but it has been referred to also as a serotoninnorepinephrine-dopamine reuptake inhibitor. In fact, it has been described that at high doses, it weakly inhibits also the reuptake of dopamine [1]. Kleptomania is an impulse control disorder characterized by the inability to resist the impulse to steal and by overincreasing tension leading up to the theft and an intense feeling of relief or gratification after [2]. Etiopathological basis of kleptomania are still unclear. Biological and psychological models have been proposed, but to date, clear causes have not been defined [3]. Here, we report the case of a 47-year-old ladywith a history of major depressive disorder. She had been taking venlafaxine (75 mg/day) for 12 months for a moderate depressive episode. At that time, she was not on any other medications. The therapy with venlafaxine produced a rapid remission of the depressive episode with a complete recovery of her working and social functioning. She did not report any adverse drug reaction (ADR) apart from mild sedation during the first week of treatment. After 12 months on venlafaxine, she was diagnosed with a uterine lesion and a hysteroscopy was programmed for the following month. The patient became very worried and anxious about the procedure, her mood started worsening, and in 2 weeks time she felt really depressed. We therefore increased venlafaxine to 150 mg/day for 10 days and then to 225 mg/day. This induced a rapid and dramatic improvement of her depressive and anxious symptoms. Nevertheless, 2 weeks later, she started developing very severe kleptomaniac thoughts and she started stealing useless objects in the supermarket and in shops. She described the presence of recurring intrusive thoughts, impotence to resist the compulsion to engage in stealing, and a release of pressure following the act. Although she initially experienced the typical very pleasant sensation of excitement, she soon felt feelings of remorse and shame. In the meantime, she had her hysteroscopy and the biopsy of her lesion revealed a benign lesion. We therefore decided to gradually decrease the dose of venlafaxine up to 75 mg/day. She remained stable from the mood point of view, but her kleptomaniac thoughts and acts suddenly stopped. On examination, 2 months later, she described the episode experienced as Bsomething I can not explain, that impulse was completely out of my control.^ This case fulfilled DSM-5 diagnostic criteria of kleptomania [4]. To the best of our knowledge, this is the first case of venlafaxine-induced kleptomania. We hypothesized that the high dose of venlafaxine (225 mg/day) has led to a reuptake also of dopamine in the frontal cortex. It is well known that a common ADR of dopamine-agonist medications is impulse control disorders (ICDs). Pathological gambling, compulsive shopping, compulsive eating, and hypersexuality are the most common ICDs described in Parkinson’s disease (PD) [5]. Although most rarely, also kleptomaniac thoughts and behaviors have been described in patients on dopamine-agonist drugs [6]. In PD, ventral striatal dopamine is preserved relative to dorsal striatal activity; thus, dopaminergic treatment titrated to alleviate motor dorsal striatal deficiencies may result in an Bover-dosing^ in ventral cortico-striatal cognitive and limbic pathways. And as such, there is preliminary evidence for the benefit of atypical * Benedetta Demartini bennidemartini@hotmail.it

Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy

Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network “Depot” Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. Results Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. Discussion LAIs’ prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs.

7 Psychogenic non-epileptic seizures and functional motor symptoms: a common aetiopathology?

Objective Recently, few studies have tried to compare patients affected by psychogenic non-epileptic seizures (PNES) and patients affected by functional motor symptoms (FMS) from a demographic, clinical and psychological angle. Nevertheless, as far as we are aware, no previous study has compared those two groups from an aetiopathological point of view. The aim of our study was to assess levels of dissociation and its subcomponents (detachment and compartmentalization), alexithymia and interoceptive sensitivity in patients with PNES and in patients with FMS. Method We conducted a cross-sectional study recruiting 20 patients with PNES, 20 patients with FMS and 20 healthy subjects as a control group. All subjects underwent: Dissociative Experience Scale (DES), Somatoform Dissociation Questionnaire SDQ-20), Cambridge Depersonalization Scale (CDS), Toronto Alexithymia Scale (TAS-20), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for anxiety (HAM-A), heart beat detection task. Results Our data suggest that PNES group scored significantly higher than the healthy control group on a measure of detachment CDS). As a result also the DES score, which is a measure of psychoform dissociation, was significantly higher that the healthy control group. On the other hand patients affected by FMS scored significantly higher than the healthy control group on a measure of compartmentalization but were no more likely to report experiences of detachment on the CDS. Our data suggest that patients affected by PNES and FMS are significantly more alexithymic than healthy controls, with a third of them patients reaching full criteria for alexithymia. Conclusion We propose a model where a different stressor (psychological for PNES and physical for FMS) leads to the development of the specific symptom through specific aetiopathological mechanisms.

A chronobiological perspective on ketamine's antidepressant efficacy.

Over the past months, several contributions on the antidepressant effect of ketamine paved the way for a fruitful debate on this compound’s mechanism of action in your Journal (Moaddel et al. 2015; Zhang et al. 2015). In order to contribute, we review the evidence linking the antidepressant efficacy of ketamine to its action on chronobiological processes that are known to be disrupted in mood disorders. In particular, recent evidence of ketamine-dependent changes to chronobiological parameters will be analyzed and a mechanism that could contribute to the antidepressant action of ketamine will be proposed.

What Are the Clinical Implications of Protoconsciousness Theory for the Conceptualization of Those Psychiatric Disorders Commonly Referred to as Mental Illnesses

J. Allan Hobson proposes that human high-order awareness, a type of meta-awareness, arose from a basic and low-order awareness (“protoconsciousness”) common to animals and humans that is primarily emotional and perceptual. Hobson also suggests that the latter is phenomenally fully expressed in the dreams of both animals and humans, whereas the former is only expressed in humans during wakefulness and is intimately related to the development of language. According to this theory, the awareness of one’s self and all related aspects of metacognition depend on the flowing of time and space related personal experiences which are stored in memory circuits after some mental elaboration mediated by linguistic abilities. In his model, the mutual relationships and influences between these two levels of human awareness must be physiologically regulated to avoid psy=chosis. In Hobson’s view, dreaming is akin to an organic psychosis (or Delirium), which is clinically distinct from the psychosis found in mental disorders such as schizophrenia or manic-depressive illness.