Highlights • Depressive disorders may represent an interactive matrix of reciprocally interactive pathophysiological mechanisms. • These biological mechanisms may reduce neuroplasticity and ...compromise the functional integrity of affect regulation neurocircuitry. • An R-Doc approach to depressive disorders is essential to understand each biological mechanism before understanding their interaction. • An overly reductionistic approach may miss the essence of the disorder, which likely lies in the complex interactions among various pathophysiological mechanisms, rather than in one mechanism in isolation. • An integrated view of the neurobiology of depression is only one hypothesis, and depressive disorders may represent several subsyndromes, or even numerous discrete disorders
Patient retrospective recollection is a mainstay of assessing symptoms in mental health and psychiatry. However, evidence suggests that these retrospective recollections may not be as accurate as ...data collection though the experience sampling method (ESM), which captures patient data in "real time" and "real life." However, the difficulties in practical implementation of ESM data collection have limited its impact in psychiatry and mental health. Smartphones with the capability to run mobile applications may offer a novel method of collecting ESM data that may represent a practical and feasible tool for mental health and psychiatry.
This paper aims to provide data on psychiatric patients' prevalence of smartphone ownership, patterns of use, and interest in utilizing mobile applications to monitor their mental health conditions.
One hundred psychiatric outpatients at a large urban teaching hospital completed a paper-and-pencil survey regarding smartphone ownership, use, and interest in utilizing mobile applications to monitor their mental health condition.
Ninety-seven percent of patients reported owning a phone and 72% reported that their phone was a smartphone. Patients in all age groups indicated greater than 50% interest in using a mobile application on a daily basis to monitor their mental health condition.
Smartphone and mobile applications represent a practical opportunity to explore new modalities of monitoring, treatment, and research of psychiatric and mental health conditions.
This article reviews the conceptual basis, definitions, and evolution of cognitive training approaches for the treatment of mental disorders.
The authors review the current state of the knowledge on ...cognitive training in psychiatric illnesses, and its neural and behavioral targets, and summarize the factors that appear to relate to a successful response, including learner characteristics that influence clinical outcome. They also discuss methodological issues relevant to the development and testing of cognitive training approaches, with the goal of creating maximally efficient and effective approaches to training. Finally, they identify gaps in existing knowledge and outline key research directions for the future.
While much of the early research has been conducted in schizophrenia, cognitive training has more recently been applied to a widening range of neuropsychiatric illnesses, including attention deficit hyperactivity disorder, mood disorders, and substance use disorders. Cognitive training harnesses the inherent neuroplastic capacities of the brain, targeting neural system function across psychiatric disorders, thus improving the cognitive processes that play a role in emotion regulation, clinical symptoms, and adaptive community functioning.
Cognitive training offers considerable promise, especially given the limited efficacy of pharmacological interventions in ameliorating cognitive deficits. However, more research is needed to understand the mechanisms underlying cognitive training, predictors of response, generalization and real-world applicability, and approaches to dissemination in practice settings.
The interpretability of results in psychiatric neuroimaging is significantly limited by an overreliance on correlational relationships. Purely correlational studies cannot alone determine whether ...behavior-imaging relationships are causal to illness, functionally compensatory processes, or purely epiphenomena. Negative symptoms (e.g., anhedonia, amotivation, and expressive deficits) are refractory to current medications and are among the foremost causes of disability in schizophrenia. The authors used a two-step approach in identifying and then empirically testing a brain network model of schizophrenia symptoms.
In the first cohort (N=44), a data-driven resting-state functional connectivity analysis was used to identify a network with connectivity that corresponds to negative symptom severity. In the second cohort (N=11), this network connectivity was modulated with 5 days of twice-daily transcranial magnetic stimulation (TMS) to the cerebellar midline.
A breakdown of connectivity in a specific dorsolateral prefrontal cortex-to-cerebellum network directly corresponded to negative symptom severity. Restoration of network connectivity with TMS corresponded to amelioration of negative symptoms, showing a statistically significant strong relationship of negative symptom change in response to functional connectivity change.
These results demonstrate that a connectivity breakdown between the cerebellum and the right dorsolateral prefrontal cortex is associated with negative symptom severity and that correction of this breakdown ameliorates negative symptom severity, supporting a novel network hypothesis for medication-refractory negative symptoms and suggesting that network manipulation may establish causal relationships between network markers and clinical phenomena.
Elevations in peripheral inflammatory markers have been reported in patients with psychosis. Whether this represents an inflammatory process defined by individual or subgroups of markers is unclear. ...Further, relationships between peripheral inflammatory marker elevations and brain structure, cognition, and clinical features of psychosis remain unclear. We hypothesized that a pattern of plasma inflammatory markers, and an inflammatory subtype established from this pattern, would be elevated across the psychosis spectrum and associated with cognition and brain structural alterations. Clinically stable psychosis probands (Schizophrenia spectrum, n = 79; Psychotic Bipolar disorder, n = 61) and matched healthy controls (HC, n = 60) were assessed for 15 peripheral inflammatory markers, cortical thickness, subcortical volume, cognition, and symptoms. A combination of unsupervised exploratory factor analysis and hierarchical clustering was used to identify inflammation subtypes. Levels of IL6, TNFα, VEGF, and CRP were significantly higher in psychosis probands compared to HCs, and there were marker-specific differences when comparing diagnostic groups. Individual and/or inflammatory marker patterns were associated with neuroimaging, cognition, and symptom measures. A higher inflammation subgroup was defined by elevations in a group of 7 markers in 36% of Probands and 20% of HCs. Probands in the elevated inflammatory marker group performed significantly worse on cognitive measures of visuo-spatial working memory and response inhibition, displayed elevated hippocampal, amygdala, putamen and thalamus volumes, and evidence of gray matter thickening compared to the proband group with low inflammatory marker levels. These findings specify the nature of peripheral inflammatory marker alterations in psychotic disorders and establish clinical, neurocognitive and neuroanatomic associations with increased inflammatory activation in psychosis. The identification of a specific subgroup of patients with inflammatory alteration provides a potential means for targeting treatment with anti-inflammatory medications.
Abstract Although dementia praecox or schizophrenia has been considered a unique disease entity for the past century, its definitions and boundaries have continued to vary over this period. At any ...given time, the changing concept of schizophrenia has been influenced by available diagnostic tools and treatments, related conditions from which it most needs to be distinguished, extant knowledge and scientific paradigms. There is significant heterogeneity in the etiopathology, symptomatology, and course of schizophrenia. It is characterized by an admixture of positive, negative, cognitive, mood, and motor symptoms whose severity varies across patients and through the course of the illness. Positive symptoms usually first begin in adolescence or early adulthood, but are often preceded by varying degrees of negative and cognitive symptomatology. Schizophrenia tends to be a chronic and relapsing disorder with generally incomplete remissions, variable degrees of functional impairment and social disability, frequent comorbid substance abuse, and decreased longevity. Although schizophrenia may not represent a single disease with a unitary etiology or pathogenetic process, alternative approaches have thus far been unsuccessful in better defining this syndrome or its component entities. The symptomatologic, course, and etio-pathological heterogeneity can usefully be addressed by a dimensional approach to psychopathology, a clinical staging approach to illness course, and by elucidating endophenotypes and markers of illness progression, respectively. This will allow an approach to the deconstruction of schizophrenia into its multiple component parts and strategies to reconfigure these components in a more meaningful manner. Possible implications for DSM-V and ICD-11 definitions of schizophrenia are discussed.
Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than ...relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations.
A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected.
Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders.
These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.
Schizophrenia (SZ) is a brain disorder that has been intensively studied for over a century; yet, its etiology and multifactorial pathophysiology remain a puzzle. However, significant advances have ...been made in identifying numerous abnormalities in key biochemical systems. One among these is the antioxidant defense system (AODS) and redox signaling. This review summarizes the findings to date in human studies. The evidence can be broadly clustered into three major themes: perturbations in AODS, relationships between AODS alterations and other systems (i.e., membrane structure, immune function, and neurotransmission), and clinical implications. These domains of AODS have been examined in samples from both the central nervous system and peripheral tissues. Findings in patients with SZ include decreased nonenzymatic antioxidants, increased lipid peroxides and nitric oxides, and homeostatic imbalance of purine catabolism. Reductions of plasma antioxidant capacity are seen in patients with chronic illness as well as early in the course of SZ. Notably, these data indicate that many AODS alterations are independent of treatment effects. Moreover, there is burgeoning evidence indicating a link among oxidative stress, membrane defects, immune dysfunction, and multineurotransmitter pathologies in SZ. Finally, the body of evidence reviewed herein provides a theoretical rationale for the development of novel treatment approaches.
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