Abstract
This invited commentary provides a conceptual history of modern early intervention services, briefly reviews the accomplishments of an international clinical and research community, and ...offers proposals for how such services might participate in the next generation of progress. In keeping with the theme of this column, we make the argument that such services should orient around bi-directional knowledge translation across basic, clinical and policy domains.
There is a large variability in the recovery trajectory and outcome of first episode of psychosis FEP patients. To date, individuals' outcome trajectories at early stage of illness and potential risk ...factors associated with a poor outcome trajectory are largely unknown. This study aims to apply three separate predictors (positive symptoms, negative symptoms, and soft neurological signs) to identify homogeneous function outcome trajectories in patients with FEP using objective data-driven methods, and to explore the potential risk /protective factors associated with each trajectory.
A total of 369 first episode patients (93% antipsychotic naive) were included in the baseline assessments and followed-up at 4–8 weeks, 6 months, and 1 year. K means cluster modeling for longitudinal data (kml3d) was used to identify distinct, homogeneous clusters of functional outcome trajectories. Patients with at least 3 assessments were included in the trajectory analyses (N = 129). The Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Neurological examination abnormalities (NEA) were used as predictors against Global Assessment of Functioning Scale (GAF).
In each of the three predictor models, four distinct functional outcome trajectories emerged: “Poor”, “Intermediate”, High” and “Catch-up”. Individuals with male gender; ethnic minority status; low premorbid adjustment; low executive function/IQ, low SES, personality disorder, substance use history may be risk factors for poor recovery.
Functioning recovery in individuals with FEP is heterogeneous, although distinct recovery profiles are apparent. Data-driven trajectory analysis can facilitate better characterization of individual longitudinal patterns of functioning recovery.
IMPORTANCE: Cognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction ...across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs. OBJECTIVE: To examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains. DESIGN, SETTING, AND PARTICIPANTS: A total of 201 healthy control participants and 375 patients with psychotic disorders from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were studied from September 29, 2007, to May 31, 2011. The B-SNIP recruited healthy controls and stable outpatients from 6 sites: Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Detroit, Michigan; and Hartford, Connecticut. All participants underwent cognitive testing and resting-state functional magnetic resonance imaging. Data analysis was performed from April 28, 2015, to February 21, 2017. MAIN OUTCOMES AND MEASURES: The Brief Assessment of Cognition in Schizophrenia was used to measure cognitive ability. A principal axis factor analysis on the Brief Assessment of Cognition in Schizophrenia battery yielded a single factor (54% variance explained) that served as the measure of general cognitive ability. Functional network integrity measures included global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network, and auditory network and exploratory analyses of all networks from the Power atlas. Group differences in network measures, associations between cognition and network measures, and mediation models were tested. RESULTS: The final sample for the current study included 201 healthy controls, 143 patients with schizophrenia, 103 patients with schizoaffective disorder, and 129 patients with psychotic bipolar disorder (mean SD age, 35.1 12.0 years; 281 male 48.8% and 295 female 51.2%; 181 white 31.4%, 348 black 60.4%, and 47 other 8.2%). Patients with schizophrenia (Cohen d = 0.36, P < .001) and psychotic bipolar disorder (Cohen d = 0.33, P = .002) had significantly reduced CON global efficiency compared with healthy controls. All patients with psychotic disorders had significantly reduced CON local efficiency, but the clinical groups did not differ from one another. The CON global efficiency was significantly associated with general cognitive ability across all groups (β = 0.099, P = .009) and significantly mediated the association between psychotic disorder status and general cognition (β = −0.037; 95% CI, −0.076 to −0.014). Subcortical network global efficiency was also significantly reduced in psychotic disorders (F3,587 = 4.01, P = .008) and positively predicted cognitive ability (β = 0.094, P = .009). CONCLUSIONS AND RELEVANCE: These findings provide evidence that reduced CON and subcortical network efficiency play a role in the general cognitive deficit observed across the psychosis spectrum. They provide new support for the dimensional hypothesis that a shared neurobiological mechanism underlies cognitive impairment in psychotic disorders.
The brain’s default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar ...disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging–genetic relationships. ICA identified three DMNs. Hypo-connectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases.
Post-traumatic stress disorder (PTSD) is a debilitating mental illness with limited treatment options and a high treatment dropout rate. Psychedelics, often in combination with psychotherapy, are now ...under investigation as a potential treatment option for a variety of psychiatric conditions including PTSD. This paper reviews the proposed mechanism of action for 3,4-Methylenedioxymethamphetamine (MDMA) and classical psychedelics such as psilocybin in treating PTSD, along with available clinical evidence, safety and side effects. MDMA-assisted psychotherapy is in FDA phase III clinical trials for PTSD and is purported to work by way of increased empathy and decreased amygdala activation during the therapeutic encounter and trauma processing. Classical psychedelics may create change by a subjective transformative experience along with an observable process of brain network alterations, though these substances have not been clinically studied in the context PTSD. In recent human-subject studies MDMA-assisted therapy resulted in significant improvement in PTSD symptoms with a good safety and side effect profile. There is not yet direct clinical evidence for classical psychedelics in treating PTSD, but the evidence supports such a trial. The studies to date have been relatively small, and participants are wellscreened for potential co-morbidities which could increase the risks of psychedelic treatment. Nonetheless, the data is promising for psychedelic-assisted treatment to become a much-needed treatment option for PTSD.
•Emerging models of the neurological and psychological effects of psychedelics provide support for their potential use in PTSD•MDMA-assisted therapy has a robust effect on PTSD symptoms with relatively minor side effects in the population studied•There is adequate evidence to support direct clinical study of psilocybin-assisted therapy for the treatment of PTSD•Safety data on psychedelics is reassuring to date, and likely to change as clinicians and patients grow in number & diversity
Abnormal neuroanatomic brain networks have been reported in schizophrenia, but their characterization across patients with psychotic disorders, and their potential alterations in nonpsychotic ...relatives, remain to be clarified. Participants recruited by the Bipolar and Schizophrenia Network for Intermediate Phenotypes consortium included 326 probands with psychotic disorders (107 with schizophrenia (SZ), 87 with schizoaffective disorder (SAD), 132 with psychotic bipolar disorder (BD)), 315 of their nonpsychotic first-degree relatives and 202 healthy controls. Single-subject gray matter graphs were extracted from structural MRI scans, and whole-brain neuroanatomic organization was compared across the participant groups. Compared with healthy controls, psychotic probands showed decreased nodal efficiency mainly in bilateral superior temporal regions. These regions had altered morphological relationships primarily with frontal lobe regions, and their network-level alterations were associated with positive symptoms of psychosis. Nonpsychotic relatives showed lower nodal centrality metrics in the prefrontal cortex and subcortical regions, and higher nodal centrality metrics in the left cingulate cortex and left thalamus. Diagnosis-specific analysis indicated that individuals with SZ had lower nodal efficiency in bilateral superior temporal regions than controls, probands with SAD only exhibited lower nodal efficiency in the left superior and middle temporal gyrus, and individuals with psychotic BD did not show significant differences from healthy controls. Our findings provide novel evidence of clinically relevant disruptions in the anatomic association of the superior temporal lobe with other regions of whole-brain networks in patients with psychotic disorders, but not in their unaffected relatives, suggesting that it is a disease-related trait. Network disorganization primarily involving frontal lobe and subcortical regions in nonpsychotic relatives may be related to familial illness risk.
The current Covid-19 pandemic is posing an unprecedented threat to global well-being and its mental health consequences are just becoming understood. While the crisis has led to a temporary halt in a ...lot of ongoing or planned psychiatric research, this pandemic is a natural experiment that can help the field to repurpose research to better understand the causes, presentations and outcome trajectories as well as treatments in psychiatry. Inter-disciplinary collaborations between researchers are needed to rapidly develop and share the emerging new knowledge of the mental health implications of Covid-19, This will help mount an effective response to the current as well as future pandemics.
Humans have asked themselves the question “who am I” from ancient times. Vedic, upanishadic and buddhist philosophers have pointed out over millennia the illusive nature of the individual self, and ...posit either a no-self, or a universal Self. Vedantic scholars also posit the illusory nature of the universe (Maya) and suggest that the only reality is the knower (Brahman), a view resonating with modern concepts in quantum theory. On the other hand, western philosophers, notably influenced by the Cartesian dualism, have pursued an individualist view of the self. Recent psychological literature is convergent with eastern views and emphasizes the importance of understanding the self, metacognition and mindful practices to understand the mind and its afflictions. Several recent western psychotherapeutic models resonate with, and may have been motivated, at least in part, by ancient eastern philosophy and spiritual practices. More work is needed to develop and implement psychotherapeutic approaches using eastern insights, and to empirically test their effectiveness.
•Eastern philosophers suggest the illusive nature of the individual self, and posit either a no-self, or a universal Self.•Eastern views emphasize the importance of understanding metacognition and mindful practices.•Several recent western psychotherapeutic models resonate with ancient eastern traditions.•Psychotherapeutic approaches based on eastern insights, need to be studied further.
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