Armando D'Agostino

Bizarreness in dream reports and waking fantasies of psychotic schizophrenic and manic patients: Empirical evidences and theoretical consequences

Several overlapping features have frequently been described between psychosis and the subjective experience of dreaming from the neurobiological to the phenomenological level, but whether this similarity reflects the cognitive organization of schizophrenic thought or rather that of psychotic mentation independent of diagnostic categories is still unclear. In this study, 40 actively psychotic inpatients were equally divided in two age- and education-matched groups according to their diagnosis (Schizophrenia and Bipolar Disorder). Participants were asked to report their dreams upon awakening and the Thematic Apperception Test (TAT) was administered to elicit waking fantasies; the same procedure was used in a control group of 20 non-psychiatric subjects. Two highly trained judges scored the collected material according to a Dream Bizarreness scale. The same level of cognitive bizarreness was found in TAT and dream reports of schizophrenic and manic subjects but was almost completely absent in the TAT stories of the control group. Two-way analysis of variance for repeated measures assessed the effect of diagnosis and experimental conditions (TAT stories and dream reports) on bizarreness yielding a significant interaction. Cognitive bizarreness seems to be a shared feature of dreaming and psychotic mentation, beyond diagnostic categorizations. Although these findings must be considered preliminary, this experimental measure of the cognitive architecture of thought processes seems to support the view that dreaming could be a useful model for the psychoses.

Sleep spindle deficit in schizophrenia: contextualization of recent findings

Sleep spindles are wax and waning brain oscillations at a frequency range of 11–16 Hz, lasting 0.5–2 s, that define non-rapid eye movement sleep stage 2. Over the past few years, several independent studies pointed to a decrease of sleep spindles in schizophrenia. The aim of this review is to contextualize these findings within the growing literature on these oscillations across other neuro-psychiatric disorders. Indeed, spindles reflect the coordinated activity of thalamocortical networks, and their abnormality can be observed in a variety of conditions that disrupt local or global thalamocortical connectivity. Although the broad methodological variability across studies limits the possibility of drawing firm conclusions, impaired spindling activity has been observed in several neurodevelopmental and neurodegenerative disorders. Despite such lack of specificity, schizophrenia remains the only condition with a typical late adolescence to young adulthood onset in which impaired spindling has been consistently reported. Further research is necessary to clearly define the pathogenetic mechanisms that lead to this deficit and the validity of its widespread use as a clinical biomarker.

Dreaming and the neurobiology of self: recent advances and implications for psychiatry.

Throughout most of the 20th century, dreaming was considered at the center of the leading psychotherapeutic approaches to mental disorders. Psychodynamic models of the mind stemmed from Sigmund Freuds Interpretation of Dreams, according to which knowledge of the unconscious foundations of most symptoms could be enhanced by an accurate evaluation of reported dreams. Toward the end of the century, these conceptualizations were challenged by a progressive shift of perspective in the direction of neurobiologically informed, mechanistic models of brain dysfunction. The diffusion of effective psychotropic medications developed to target specific symptoms across different disorders contributed to the requalification of psychiatry itself within the broader domain of medical sciences. A whole generation of psychiatrists turned to biology as a more scientific, rigorous and reliable framework to understand mental disorders. In parallel, new psychological techniques began to emerge that aimed to treat symptoms more directly by addressing dysfunctional cognitive constructs, leading to a relative weakening of the psychodynamic paradigm that is now considered one of several possible models in need of a neuroscientific validation. Neuroscience itself is largely based on cognitive psychology given the major simplicity of its theories in comparison to psychodynamic models, so that neurobiological research paradigms in psychiatry aim to define neural substrates of cognitive mechanisms that differ from the norm (Fusar-Poli and Broome, 2006). In line with this progression of scientific thought, modern dream research in psychiatry focuses on abnormalities of manifest dream content that can be found within different disorders. Although Post-Traumatic Stress Disorder (PTSD) is the only condition within which specific abnormalities of dream content are considered by clinicians in the diagnostic process—and become a specific target of treatment—several studies have shown that abnormal, disorder-specific dreams are reported by most subjects diagnosed with a mental disorder (Beauchemin and Hays, 1995; Sauteraud and Menny, 1997; Schredl and Engelhardt, 2001; Cartwright et al., 2006; Lusignan et al., 2009). Although several hypotheses on the relationship between dream and waking experiences have been proposed, some of which based on the known abnormalities of sleep rhythms and architecture that occur in psychiatric disorders, no definitive conclusion can be drawn. This difficulty relates to a poor understanding of mechanistic links between psychiatric diagnoses, sleep abnormalities, and chronobiological disruptions that have been recognized and studied for many decades (Wulff et al., 2010). In this opinion article, we will propose that the progressive refinement of our understanding of dream consciousness could foster significant advances for neuroscience and psychiatry as a whole.

The dreaming brain/mind: a role in understanding complex mental disorders?

Abnormalities in the sleep/wake cycle and within sleep itself have extensively been studied in a broad range of psychiatric and neurodegenerative disorders. Despite increasing evidence for a mechanistic overlap between the disruptions of circadian timing control and neuropathology, the relationship remains unclear (Wulff et al., 2010). One possible way to address this problem from a psychiatric perspective is to compare the phenomenological correlate of sleep with the waking mentation observed in patients. Indeed, so-called “positive” symptoms such as abnormal senso-perceptual experiences or thought processes ranging from ideas of reference to highly structured delusions, share substantial similarities with dream phenomenology. The same process by which psychotic patients progress from salience attributed to irrelevant stimuli to a new, highly relevant meaning, appears to occur in dreams, where a single hallucinatory image can convey “an immediate emotionally compelling meaning that is not related to the image in any obvious way” (Feinberg, 2011). With the exception of the rare experience of lucidity, the dreamer has no recognition of his objective status, i.e., being asleep and vastly detached from the external environment; dream images produced uniquely by endogenous neural activity are interpreted as coming from the external world; heightened and often incongruous emotions are coupled with a decrease in ego functions which ultimately leads to instinctual behaviors and severe impairment in reality testing (Hobson, 2009). The striking similarity between these aspects of dreaming and psychosis has been observed by most of the funding pioneers of the modern approach to psychopathology. Indeed, it is largely unknown that Emil Kraepelin extensively studied his own dreams with the aim of progressing his understanding of schizophrenic thought disorder (Engels et al., 2003). Recent advances in neuroscience have led few contemporary researchers to bind these complex phenomena, with electrophysiological, neurochemical, and cerebrofunctional data now pointing to shared patterns across dreaming and psychotic experiences (Hobson, 2004; Gottesmann, 2006).

Psychogenic non-epileptic seizures and functional motor symptoms : A common phenomenology?

OBJECTIVE Recent studies have attempted to compare patients affected by psychogenic non-epileptic seizures (PNES) to patients affected by functional motor symptoms (FMS) from a demographic, clinical and psychological perspective. Nevertheless, results are quite controversial and significant conclusions have not been drawn. The aim of our study was to evaluate the phenomenology of psychology of the two groups assessing levels of dissociation and its subcomponents, alexithymia and interoceptive sensitivity in patients with PNES and in patients with FMS. METHODS 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). Also at the DES, a measure of psychoform dissociation, PNES patients scored significantly higher than healthy subjects. On the other hand patients affected by FMS scored significantly higher than the healthy control group on the SDQ but they did not report more experiences of detachment on the CDS. Patients affected by PNES and FMS were significantly more alexithymic than healthy controls, with a third of them scoring >61 on the TAS-20. SIGNIFICANCE Our data show different psychological mechanisms underlying patients with PNES and patients with FMS. This might lead also to potential implications for treatment.

Right hemisphere neural activations in the recall of waking fantasies and of dreams

The story‐like organization of dreams is characterized by a pervasive bizarreness of events and actions that resembles psychotic thought, and largely exceeds that observed in normal waking fantasies. Little is known about the neural correlates of the confabulatory narrative construction of dreams. In this study, dreams, fantasies elicited by ambiguous pictorial stimuli, and non‐imaginative first‐ and third‐person narratives from healthy participants were recorded, and were then studied for brain blood oxygen level‐dependent functional magnetic resonance imaging on a 3.0‐Tesla scanner while listening to their own narrative reports and attempting a retrieval of the corresponding experience. In respect to non‐bizarre reports of daytime activities, the script‐driven recall of dreams and fantasies differentially activated a right hemisphere network including areas in the inferior frontal gyrus, and superior and middle temporal gyrus. Neural responses were significantly greater for fantasies than for dreams in all regions, and inversely proportional to the degree of bizarreness observed in narrative reports. The inferior frontal gyrus, superior and middle temporal gyrus have been implicated in the semantic activation, integration and selection needed to build a coherent story representation and to resolve semantic ambiguities; in deductive and inferential reasoning; in self‐ and other‐perspective taking, theory of mind, moral and autobiographical reasoning. Their degree of activation could parallel the level of logical robustness or inconsistency experienced when integrating information and mental representations in the process of building fantasy and dream narratives.

Establishment of an induced pluripotent stem cell (iPSC) line from a patient with Clozapine-responder Schizophrenia

Peripheral blood mononuclear cells (PBMCs) were collected from a patient with treatment-refractory Schizophrenia who presented an exceptional clinical response to Clozapine. iPSC lines were established with a non-integrating reprogramming system based on Sendai virus. A footprint-free hiPSC line was characterized to confirm the expression of the main endogenous pluripotency markers and have a regular karyotype. Pluripotency was confirmed by differentiation into cells belonging to the three germ layers. This hiPSC line represents a valuable tool to study the molecular, biochemical and electrophysiological properties of mature neuronal populations belonging to Clozapine responder patients with a severe form of Schizophrenia.

Schizophrenia: from neurophysiological abnormalities to clinical symptoms

Schizophrenia (SCZ) has long been associated with multifaceted dysfunctions and multiple genetic as well as environmental etiological factors (Rethelyi et al., 2013). Therefore, after a century of inconsistent results, the search for a unifying pathogenetic mechanism has become one of the most challenging issues in SCZ research. During the last decade, a growing literature has pointed to the so-called disconnection hypothesis (Friston, 1998; Tononi and Edelman, 2000; Stephan et al., 2009), i.e., to a defective integration among distributed brain areas, which may lead to a systematic impairment of information processing. EEG is a suitable tool to probe this hypothesis in the time domain, since the EEG oscillatory activity can capture subtle functional changes of underlying neuronal systems with exquisite temporal resolution. Consistent with this prediction, several recent EEG findings have shown abnormalities in SCZ neural oscillations during both wakefulness (Uhlhaas and Singer, 2014) and sleep (Gardner et al., 2014). Cognitive and theoretical approaches of brain functioning have been used to explain phenomenological features and neural disruptions in SCZ. Since its earliest conceptualizations, abnormalities of self-experience have been identified as a critical feature of the illness (Schneider, 1950). Positive and passivity symptoms in SCZ have been hypothesized to involve a misattribution of self-generated actions, thoughts and percepts to an external agency (Frith, 2005). One possible neurophysiological explanation for this peculiar subjective experience is an aberrant generation of corollary discharge (CD) by efference copy mechanisms (Feinberg, 2011). More recently, predictive coding theories began to add an integrated and structured framework to previous observations (Van de Cruys et al., 2014; Moran et al., 2015). We herein attempt to reconcile recent major neurophysiological findings with currently established approaches to SCZ psychopathology.

Sleep spindles and slow waves in schizophrenia and related disorders: main findings, challenges and future perspectives

Sleep abnormalities have recently gained renewed attention in patients diagnosed with schizophrenia. Disrupted thalamocortical brain oscillations hold promise as putative biomarkers or endophenotypes of the disorder. Despite an increase in studies related to sleep spindle and slow‐wave activity, findings remain in part contradictory. Although sleep spindle deficits have been confirmed in several groups of patients with chronic, medicated schizophrenia, data on the early stages of the disorder and in unmedicated subjects are still insufficient. Findings on slow‐wave abnormalities are largely inconclusive, possibly due to the different criteria employed to define the phenomenon and to the influence of atypical antipsychotics. In this review, we aim to address the methodological and practical issues that may have limited the consistency of findings across research groups and different patient populations. Given the neurobiological relevance of these oscillations, which reflect the integrity of thalamocortical and cortico‐cortical function, research in this domain should be encouraged. To promote widespread consensus over the scientific and clinical implications of these sleep‐related phenomena, we advocate uniform and sound methodological approaches. These should encompass electroencephalographic recording and analysis techniques but also selection criteria and characterization of clinical populations.

From conversion disorder (DSM-IV-TR) to functional neurological symptom disorder (DSM-5): When a label changes the perspective for the neurologist, the psychiatrist and the patient

The term “conversion disorder”, as used in DSM-IV-TR, describes symptoms such as weakness, epileptic-type attacks, abnormal movements or sensory disturbance that are not attributable to a structural damage to the nervous system or to feigning and that are considered to be associated with psychological factors [1]. The traditional label “conversion disorder” refers to a hypothesis based on a psychological aetiology. In fact, historically, psychological and emotional factors, such as trauma, conflict or distress, have been suggested as causal factors of conversion disorders [2]. This explanation is also reflected in the various alternative terms used to describe these disorders, such as psychological, psychogenic, psychosomatic, or even hysteria. Distress and psychological trauma are indeed seen at higher rates in these patients than the healthy population, but recently they have not been found to be either sensitive or specific markers [3]. Thus, an alternative, perhaps equally problematic terminology focuses on what patients do not have (non-organic, medically unexplained symptoms) [4]. Indeed, the related debates regarding the “psychogenic” or “non-organic” causes of these disorders portray a compartmentalized, dualistic brain andmind relation that has not been supported by centuries of scientific research. Although long dominant, the psychodynamic hypothesis is now just one of the many competing etiological hypotheses and has little supportive empirical evidence. This is why a new (but not new) term (functional neurological symptoms) has been recently coined in order to give amore proper and respectable definition to these symptoms. The adjective “functional” refers to the main characteristic of these symptoms, namely that normal function is always possible; on the other hand it does not provide any causal link either to psychological or to any other possible aetiological factors, focusing more on “how” symptoms might be produced than on “why” [5–7]. As a result, there has been a reduced emphasis on psychological and emotional events prior to the development of symptoms (i.e. sexual abuse, remote or recent life events). Indeed, several studies have demonstrated that such traumatic events, although clearly important, might not play a unique role in the aetiology of these symptoms [3].