Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (RAs) mimic naturally occurring GLP-1 and GIP and are highly effective anti-diabetic and anti-obesity agents. In addition to their robust acute and long-term effects on weight, metabolism, and blood pressure, these agents also reduce cardiovascular mortality as well as stroke risk and associated consequences. A replicated and convergent body of preclinical evidence also indicates that incretin receptor agonists activate molecular effectors critical to neuroplasticity, neuroprotection, and anti-apoptosis. Herein, we propose that GLP-1 RAs and GIP RAs are promising transdiagnostic mechanistically informed therapeutics in the treatment and prevention of multiple domains of psychopathology, including general cognitive, reward, and motivation systems and mental disorders. Major neurocognitive disorders (eg, Alzheimer’s Disease, Parkinson’s Disease), alcohol and substance use disorders, traumatic brain injury, and depressive disorders are near-term therapeutic targets. In addition, GLP-1 RAs and GIP RAs have robust effects on comorbidities that differentially affect persons with mental disorders (eg, cardiovascular, cerebrovascular, and metabolic disorders) and psychotropic drug-related weight gain.

The link between creativity and serious mental illness (SMI) is widely discussed. Jackson Pollock is one example of a giant in the field of art who was both highly creative and experiencing an SMI. Pollock created a new genre of art known as abstract expressionism (“action painting”) defined as showing the frenetic actions of painting. The question arises whether his SMI played any role in the way he created his drip paintings, especially when he was overactive and manic. Furthermore, did visual hallucinations or enhanced visual perception associated with mania or psychosis facilitate Pollock in embedding and camouflaging images under layers of thrown paint? Seeing images in Pollocks drip paintings has been a controversy ever since these paintings were created. Some experts attribute this to pareidolia—perceiving specific images out of random or ambiguous visual patterns—a phenomenon known to be enhanced by fractal fuzzy edges such as seen in Rorschach ink blots as well as in Pollock drip paintings. So, are Pollock’s drip paintings merely giant Rorschach images, or did Pollock insert polloglyphs—images that are encrypted that tell a story about Pollock’s inner being—into his paintings and then disguise them with drippings? Here, we explore answers to these questions and discuss images that Pollock included in his earliest sketches and used repeatedly in his abstract paintings and later in his drip paintings to argue that these images are not accidental.

Experts have been fascinated with Jackson Pollock (born 1912, died 1956) and his famous “drip paintings” ever since he began producing them in the 1940s. It is well documented that Pollock began to have mood swings as a child, with symptoms of social anxiety relieved by alcoholic binges from his teen years until his death. He received psychoanalytic psychotherapy, psychiatric hospitalization and some psychopharmacologic treatments from age 23 until his death at age 44. Most of his treatment was by psychiatrists trained in Jungian or Freudian psychoanalysis. Pollock was first hospitalized at New York Westchester Hospital in 1938 with his first “breakdown,” likely a manic/hypomanic or psychotic episode combined with alcohol intoxication. Without modern antipsychotic medications or lithium at the time, he was allowed to rest and improve and at that time was tested extensively with Rorschach ink blots, a new technology at the time, and which undoubtedly influenced the Polloglyphs embedded in his later works.

Pollock was afflicted with hallucinatory spells, particularly visual. With his eyes wide open, he would suddenly begin to see whirling images, and Pollock himself realized that for his drip paintings he had seen those images before he painted them. Bipolar experts have written about altered sensory phenomena experienced in bipolar disorder and even theorized a suprasensory world for some patients with enhanced visual perceptual abilities especially when manic or hypomanic. Although Jackson according to his biographers was variably diagnosed as “alcoholic psychosis,” “schizoid” or “a schizophrenia like disorder characterized by alternating periods of violent agitation and paralysis or withdrawal,” in today’s world he would more likely be diagnosed as bipolar. This is supported by other comments from his biography that “more and more the schizophrenic like state described by his psychiatrist was playing itself out in a binary drama of depression and elation.” His older brother Charles was hospitalized in 1942 for a “nervous breakdown” possibly a bipolar episode, suggesting a positive family history of bipolar disorder in the Pollock family.

About 1947 he began his drip paintings and his longest period of uninterrupted productivity until about 1950. During this period, he created his masterpieces, especially during the years between 1948 and 1950, a time when he drank little and was treated with the early mood stabilizers Dilantin and phenobarbital. He stopped his meds and eventually crashed his car after drinking and died at age 44. Experts have long pondered the relationship between creativity/genius and bipolar disorder. For Pollock, the Polloglyphs in his drip paintings seem to be linked to his creativity and genius shaped by bipolar disorder thus expressing his inner emotions as camouflaged images on canvas.

Schizophrenia spectrum disorders are brain diseases that are developmental dementias (dementia praecox). Their pathology begins in utero with psychosis most commonly becoming evident in adolescence and early adulthood. It is estimated they afflict the U.S. population at a prevalence rate of approximately 0.8%. Genetic studies indicate that these brain diseases are about 80% determined by genes and about 20% determined by environmental risk factors. Inheritance is polygenic with some 270 gene loci having been identified as contributing to the risk for schizophrenia. Interestingly, many of the identified gene loci and gene polymorphisms are involved in brain formation and maturation. The identified genetic and epigenetic risks give rise to a brain in which neuroblasts migrate abnormally, assume abnormal locations and orientations, and are vulnerable to excessive neuronal and synaptic loss, resulting in overt psychotic illness. The illness trajectory of schizophrenia then is one of loss of brain mass related to the number of active psychotic exacerbations and the duration of untreated illness. In this context, molecules such as dopamine, glutamate, and serotonin play critical roles with respect to positive, negative, and cognitive domains of illness. Acutely, antipsychotics ameliorate active psychotic illness, especially positive signs and symptoms. The long-term effects of antipsychotic medications have been debated; however, the bulk of imaging data suggest that antipsychotics slow but do not reverse the illness trajectory of schizophrenia. Long-acting injectable antipsychotics (LAI) appear superior in this regard. Clozapine remains the “gold standard” in managing treatment-resistant schizophrenia.

Alzheimer’s dementia (AD) is a progressive, neurodegenerative disease often accompanied by neuropsychiatric symptoms that profoundly impact both patients and caregivers. Agitation is among the most prevalent and distressing of these symptoms and often requires treatment. Appropriate therapeutic interventions depend on understanding the biological basis of agitation and how it may be affected by treatment. This narrative review discusses a proposed pathophysiology of agitation in Alzheimer’s dementia based on convergent evidence across research approaches. Available data indicate that agitation in Alzheimer’s dementia is associated with an imbalance of activity between key prefrontal and subcortical brain regions. The monoamine neurotransmitter systems serve as key modulators of activity within these brain regions and circuits and are rendered abnormal in AD. Patients with AD who exhibited agitation symptoms during life have alterations in neurotransmitter nuclei and related systems when the brain is examined at autopsy. The authors present a model of agitation in Alzheimer’s dementia in which noradrenergic hyperactivity along with serotonergic deficits and dysregulated striatal dopamine release contribute to agitated and aggressive behaviors.

Changing practice patterns caused by the pandemic have created an urgent need for guidance in prescribing stimulants using telepsychiatry for attention-deficit hyperactivity disorder (ADHD). A notable spike in the prescribing of stimulants accompanied the suspension of the Ryan Haight Act, allowing the prescribing of stimulants without a face-to-face meeting. Competing forces both for and against prescribing ADHD stimulants by telepsychiatry have emerged, requiring guidelines to balance these factors. On the one hand, factors weighing in favor of increasing the availability of treatment for ADHD via telepsychiatry include enhanced access to care, reduction in the large number of untreated cases, and prevention of the known adverse outcomes of untreated ADHD. On the other hand, factors in favor of limiting telepsychiatry for ADHD include mitigating the possibility of exploiting telepsychiatry for profit or for misuse, abuse, and diversion of stimulants. This Expert Consensus Group has developed numerous specific guidelines and advocates for some flexibility in allowing telepsychiatry evaluations and treatment without an in-person evaluation to continue. These guidelines also recognize the need to give greater scrutiny to certain subpopulations, such as young adults without a prior diagnosis or treatment of ADHD who request immediate-release stimulants, which should increase the suspicion of possible medication diversion, misuse, or abuse. In such cases, nonstimulants, controlled-release stimulants, or psychosocial interventions should be prioritized. We encourage the use of outside informants to support the history, the use of rating scales, and having access to a hybrid model of both in-person and remote treatment.