Gerrit I. van Schalkwyk

An Integrated Neuroscience Perspective on Formulation and Treatment Planning for Posttraumatic Stress Disorder: An Educational Review

Importance Posttraumatic stress disorder (PTSD) is a common psychiatric illness, increasingly in the public spotlight in the United States due its prevalence in the soldiers returning from combat in Iraq and Afghanistan. This educational review presents a contemporary approach for how to incorporate a modern neuroscience perspective into an integrative case formulation. The article is organized around key neuroscience “themes” most relevant for PTSD. Within each theme, the article highlights how seemingly diverse biological, psychological, and social perspectives all intersect with our current understanding of neuroscience. Observations Any contemporary neuroscience formulation of PTSD should include an understanding of fear conditioning, dysregulated circuits, memory reconsolidation, epigenetics, and genetic factors. Fear conditioning and other elements of basic learning theory offer a framework for understanding how traumatic events can lead to a range of behaviors associated with PTSD. A circuit dysregulation framework focuses more broadly on aberrant network connectivity, including between the prefrontal cortex and limbic structures. In the process of memory reconsolidation, it is now clear that every time a memory is reactivated it becomes momentarily labile—with implications for the genesis, maintenance, and treatment of PTSD. Epigenetic changes secondary to various experiences, especially early in life, can have long-term effects, including on the regulation of the hypothalamic-pituitary-adrenal axis, thereby affecting an individual’s ability to regulate the stress response. Genetic factors are surprisingly relevant: PTSD has been shown to be highly heritable despite being definitionally linked to specific experiences. The relevance of each of these themes to current clinical practice and its potential to transform future care are discussed. Conclusions and Relevance Together, these perspectives contribute to an integrative, neuroscience-informed approach to case formulation and treatment planning. This may help to bridge the gap between the traditionally distinct viewpoints of clinicians and researchers.

Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies

ABSTRACT Cognitive dysfunction in schizophrenia (SCZ) and Alzheimers disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive dysfunction relevant to both disorders suggest the &agr;7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown. To compare effect sizes between rodent and human studies, we searched PubMed and the Cochrane Library for all randomized, placebo‐controlled trials of compounds with pharmacological activity at the &agr;7 nAChR for treatment of cognitive dysfunction in SCZ and AD and identified 18 studies comprising 2670 subjects treated with eight different compounds acting as full or partial agonists. Cognitive outcomes were standardized, and random‐effects meta‐analyses revealed no statistically significant effects of &agr;7 nAChR agonists on overall cognition or any of eight cognitive subdomains when all doses were included (Range of all cognitive outcomes: Cohens d = − 0.077 to 0.12, negative favoring drug). In contrast, analysis of 29 rodent studies testing the same &agr;7 agonists revealed large effect sizes in multiple commonly used preclinical behavioral tests of cognition (Range: d = − 1.18 to – 0.73). Our results suggest that targeting the &agr;7 nAChR with agonists is not a robust treatment for cognitive dysfunction in SCZ or AD and necessitate a better understanding of the translational gap for therapeutics targeting the &agr;7 nAChR. HIGHLIGHTSNovel drugs to improve cognition in schizophrenia and Alzheimers disease are needed.The &agr;7 nicotinic receptor is a potential drug target to treat cognitive dysfunction.Meta‐analyses find large effect sizes of &agr;7 agonists in rodent cognitive studies.Meta‐analyses find no or limited effects of &agr;7 agonists on human subject cognition.Significant translational barriers exist for &agr;7 nicotinic receptor‐targeting drugs.

Reduction of Aggressive Episodes after Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder.

Aggression remains a major cause of morbidity in patients with autism spectrum disorder (ASD). Current pharmacotherapy for aggression is not always effective and is often associated with morbidity. Nicotinic acetylcholinergic neurotransmission may play a prominent role in ASD pathophysiology based on human and animal studies, and preclinical studies show nicotine administration can reduce aggression-related behaviors. Transdermal nicotine has been used to treat agitation in neuropsychiatric conditions with cholinergic dysfunction. Here we report the use of transdermal nicotine as an adjunctive medication to treat aggression in a hospitalized adolescent with ASD. Nicotine patch was recurrently well tolerated, and reduced the need for emergency medication and restraint. These findings suggest further study of transdermal nicotine for aggression comorbid with ASD is warranted.

Varieties of Misdiagnosis in ASD: An Illustrative Case Series

The relationship between autism spectrum disorders (ASD) and psychotic disorders (PD) is a focus of continued interest. There are substantial conceptual and clinical difficulties associated with diagnosing comorbid PD in individuals who have ASD. In this case series, we report on five cases where adolescents with previously diagnosed ASD were also diagnosed as psychotic. In each case, we found that these patients’ ‘psychotic’ symptoms could be better understood as a part of their underlying ASD diagnosis, with significant implications for treatment, prognosis, and access to services. This misdiagnosis likely represents a combination of adult psychiatrists being relatively inexperienced with this population, and the system of care requiring providers to apply diagnostic labels to justify inpatient hospitalization.

The formation of marijuana risk perception in a population of substance abusing patients

Risk perception has been shown to be protective with regard to marijuana use. Notably, the risk perception of marijuana in individuals with substance abuse problems varies significantly from that of the general public. Understanding how risk perception is formed in substance users could explain these differences and help predict the consequences of policy changes. Using this framework, we explored risk perception and its formation in a sample of substance abusing veterans. Semi-structured interviews were conducted with veterans who were receiving treatment for substance abuse. Interviews were recorded digitally, transcribed verbatim, and analyzed using inductive thematic analysis. A prominent perspective among the 31 participants was that marijuana is significantly different from other drugs because it is safe, not addictive, not associated with physical withdrawal, and has less overt behavioral effects than other substances. Many of these participants drew upon their own innocuous experiences with the drug in developing this perspective, more so than information from any other source. A contrasting narrative emphasized marijuana’s capacity to cause negative social consequences, act as a gateway to the use of other, more harmful substances, and cause paranoia or worsen psychosis. In conclusion, individual experience with marijuana featured more prominently in informing risk perception than any other source of information. Our results and previous literature suggest that the significant disconnect between the individual experiences of substance users and the current clinical and legal policy towards marijuana may weaken the legitimacy of public policy or the authority of the medical community.

Autism Spectrum Disorders: Challenges and Opportunities for Transition to Adulthood

Improved outcomes for individuals with autism spectrum disorder (ASD) have opened a range of potential pathways during the transition to adulthood. These include attending college, entering the labor force, and achieving a degree of independent living. Less cognitively able individuals may be eligible for state benefits and may enter supported employment programs. Those attending college require careful support and planning. Practitioners need to be familiar with the unique needs of young adults with ASD. Further research should attempt to define the priorities of individuals and families with ASD making this transition and clarify the value of existing supports and interventions.

College students with autism spectrum disorders: A growing role for adult psychiatrists.

ABSTRACT Objective: Adolescents with autism spectrum disorders (ASD) are increasingly attending college. This case report highlights the nature of the psychiatric difficulties these individuals may face and the potential role for college mental health practitioners. Participants: A case of a female student with ASD presenting with significant inattentive symptoms. Methods: The authors describe the unique features of this patients clinical presentation, discuss relevant diagnostic considerations, and make recommendations about how to best approach treatment. Results: This student presented with symptoms of attention-deficit/hyperactivity disorder (ADHD), which were first relevant during her time at college, owing to increased demands on planning and other executive functions. She was eventually responsive to treatment with a stimulant, but had more side effects early on. Conclusions: As individuals with ASD attend college, their mental health needs will require treatment. However, such treatment draws on a comparatively limited evidence base, and providers need to be aware of potential challenges that may arise.

Toward understanding the heterogeneity in obsessive-compulsive disorder: Evidence from narratives in adult patients

Background: Current attempts at understanding the heterogeneity in obsessive-compulsive disorder have relied on quantitative methods. The results of such work point toward a dimensional structure for obsessive-compulsive disorder. Existing qualitative work in obsessive-compulsive disorder has focused on understanding specific aspects of the obsessive-compulsive disorder experience in greater depth. However, qualitative methods are also of potential value in furthering our understanding of obsessive-compulsive disorder heterogeneity by allowing for open-ended exploration of the obsessive-compulsive disorder experience and correlating identified subtypes with patient narratives. Objective: We explored variations in patients’ experience prior to, during and immediately after performing their compulsions. Method: Semi-structured interviews were conducted with 20 adults with obsessive-compulsive disorder, followed by inductive thematic analysis. Participant responses were not analyzed within the context of an existing theoretical framework, and themes were labeled descriptively. Results: The previous dichotomy of ‘anxiety’ vs ‘incompleteness’ emerged organically during narrative analysis. In addition, we found that some individuals with obsessive-compulsive disorder utilized their behaviors as a way to cope with stress and anxiety more generally. Other participants did not share this experience and denied finding any comfort in their obsessive-compulsive behaviors. The consequences of attentional difficulties were highlighted, with some participants describing how difficulty focusing on a task could influence the need for it to be repeated multiple times. Conclusions: The extent to which patients use obsessive-compulsive disorder as a coping mechanism is a relevant distinction with potential implications for treatment engagement. Patients may experience ambivalence about suppressing behaviors that they have come to rely upon for management of stress and anxiety, even if these behaviors represent symptoms of a psychiatric illness.

Autism Spectrum Disorders: In Theory and Practice.

Autism is a prevalent and strongly genetic brain-based disorder. Early focus in the field on the relevance of psychogenic factors led to the blaming of parents for the occurrence of the disorder, and as a result mainstream research on psychotherapeutic approaches has until recently been limited. Although psychoanalytic approaches continue to be considered of limited relevance for these individuals, dynamic theory is both informative and informed by conceptual approaches to the understanding of autism. Theory of mind in particular is a prominent model for understanding the core deficits of autism and bears strong resemblance to the concept of mentalization. Although cognitive-behavioral and social skills interventions may form the cornerstone of psychotherapy for individuals with autism, the formation of a treatment alliance remains crucial and may require a particular willingness for flexibility on the part of the therapist.

A Predictive Coding Account of Psychotic Symptoms in Autism Spectrum Disorder

The co-occurrence of psychotic and autism spectrum disorder (ASD) symptoms represents an important clinical challenge. Here we consider this problem in the context of a computational psychiatry approach that has been applied to both conditions—predictive coding. Some symptoms of schizophrenia have been explained in terms of a failure of top–down predictions or an enhanced weighting of bottom–up prediction errors. Likewise, autism has been explained in terms of similar perturbations. We suggest that this theoretical overlap may explain overlapping symptomatology. Experimental evidence highlights meaningful distinctions and consistencies between these disorders. We hypothesize individuals with ASD may experience some degree of delusions without the presence of any additional impairment, but that hallucinations are likely indicative of a distinct process.