Mental disorders represent a public health challenge of staggering proportions. In the most recent Global Burden of Disease study, mental and substance abuse disorders constitute the leading source of years lost to disability from all medical causes ( 1 ). The World Health Organization estimates over 800,000 suicides each year globally, nearly all of which are a consequence of a mental disorder ( 2 ). These high morbidity and mortality figures speak to the potential for overall health gains if mental disorders can be more effectively diagnosed and treated. Could a “precision medicine” approach find traction here?

https://science.sciencemag.org/content/sci/348/6234/499.full.pdf

Brain disorders? Precisely

Thoroughly updated and completely reorganized for a sharper clinical focus, the Fifth Edition of this world-renowned classic synthesizes the latest advances in basic neurobiology, biological psychiatry, and clinical neuropsychopharmacology. The book establishes a critical bridge connecting new discoveries in molecular and cellular biology, genetics, and neuroimaging with the etiology, diagnosis, and treatment of the full spectrum of neuropsychiatric disorders.

Neuropsychopharmacology: The Fifth Generation of Progress

https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(13)00134-X.pdf

Mechanisms of dopamine transporter regulation in normal and disease states

Neurobiological abnormalities associated with psychiatric disorders do not map well to existing diagnostic categories. High co-morbidity suggests dimensional circuit-level abnormalities that cross diagnoses. Here we seek to identify brain-based dimensions of psychopathology using sparse canonical correlation analysis in a sample of 663 youths. This analysis reveals correlated patterns of functional connectivity and psychiatric symptoms. We find that four dimensions of psychopathology – mood, psychosis, fear, and externalizing behavior – are associated (r = 0.68–0.71) with distinct patterns of connectivity. Loss of network segregation between the default mode network and executive networks emerges as a common feature across all dimensions. Connectivity linked to mood and psychosis becomes more prominent with development, and sex differences are present for connectivity related to mood and fear. Critically, findings largely replicate in an independent dataset (n = 336). These results delineate connectivity-guided dimensions of psychopathology that cross clinical diagnostic categories, which could serve as a foundation for developing network-based biomarkers in psychiatry. Co-morbidity and symptom overlap make it difficult to associate psychiatric disorders with unique neural signatures. Here, the authors use a data-driven approach to show that the symptom dimensions of mood, psychosis, fear and externalizing behavior exhibit unique patterns of functional dysconnectivity.

/pdf/linked-dimensions-of-psychopathology-and-connectivity-in-2qqcp5m5s1.pdf

Linked dimensions of psychopathology and connectivity in functional brain networks.

Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.

Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: Update on recommendations from the British Association for Psychopharmacology

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

/pdf/reward-circuitry-dysfunction-in-psychiatric-and-16n7qg22ck.pdf

Cara A Damiano

Papers

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.