Self—the “I” we experience as our identities; in our bodies; with our histories and future possibilities; our personalities, our moment-to-moment experiences of ourselves, our environment, and relationships; our ability to decide and act; and our awareness of all this—is one of the great mysteries of philosophy and science.

A rich psychoanalytic literature has explored the psychology of the self since Heinz Kohut’s pioneering work a half century ago. Psychoanalytic self psychology is fundamentally relational: the child’s self is considered to emerge in the parent-child relationship, and self pathology can only be observed and treated by looking at its manifestations in relationships. In recent years, social neuroscientists have begun to look for underpinnings of this relational self in the biology of the brain; an example is Aikaterini Fotopoulou’s and Manos Tsakris’s recent argument of social contributions to the development of at least some of the body’s self-regulatory mechanisms....

Back in March I discussed bipolar disorder’s very complex biology, which includes abnormalities in glial-neuronal interactions, immune cells and inflammatory processes throughout the brain and body, the hypothalamic-pituitary axis, a host of genes, and several neurotransmitter systems. Here I will look at what neuroimaging tells us about abnormalities in brain regions and their connections, and then at what and advanced statistical approach to analyzing fMRI data says about the biology of emotion.

In a 2014 review, Mary Phillips and Holly Swartz of the University of Pittsburgh discussed what was known from fMRI, volumetric analyzes, diffusion imaging, and resting state techniques. Most of the studies imaged patients in the euthymic state; few included manic or depressed subjects because of the many practical difficulties conducting this type of research, including the problems disturbed patients experience cooperating with often lengthy and uncomfortable scanning procedures. Experimen...

Bipolar disorder continues to present many problems for psychiatrists, starting with the diagnosis itself. Since Kraepelin first distinguished manic depressive insanity from dementia praecox late in the nineteenth century, our concept of “pure” bipolar disorder, now called bipolar I, in which episodes of mania and depression alternate with periods of functioning has changed little. But extensive research and clinical experience have taught us that the clinical picture is more complicated: so-called mixed states and rapid cycling are common, most patients spend more time depressed than manic, and many patients have problematic mood elevation or instability but do not meet criteria for any of the three DSM diagnoses of bipolar I, bipolar II, and cyclothymic disorders. Hagop Akiskal has proposed a classification  of several more “bipolar spectrum” syndromes with more subtle mood shifts and possible comorbidity with anxiety disorders.

In practical terms, this diagnostic fuzziness can make i...

For centuries, insanity and creativity have been linked in the popular imagination. In the modern era, biographical studies of accomplished artists, as well as psychological studies of both creative individuals and psychiatric patients, have documented a correlation of bipolar disorder with creativity.

What accounts for this association? The U.C. Berkeley psychologist Sheri Johnson and a group of colleagues have looked at the psychological literature to understand what features of bipolar disorder account for creativity and what aspects of creativity are heightened in people with bipolar disorder. Their review is a good starting place to understand this fascinating connection.  

The authors wisely distinguish bipolar I disorder on the one hand from bipolar II disorder and cyclothymia on the other, which they call “bipolar spectrum” disorders. (Hagop Akiskil and others have written about a much broader bipolar spectrum which includes milder tendencies toward intense or variable mood...

Psychiatric patients usually meet diagnostic criteria for more than one disorder. Such “comorbidity” always raises questions of what causes what, for if one problem underlies the other, clinicians can hope that treating the first will resolve both. Although in practice problems tend to have lives of their own and require their own treatments, an understanding of how patients’ disorders relate to each other provides an explanatory narrative for patients and clinicians as they consider their options.

Arpana Agrawal, a geneticist at Washington University, and Michael Lynskey, who studies addiction at King’s College London, have described several genetic approaches  to the co-occurrence of cannabis use disorder with other psychiatric disorders. Their work is interesting because it extends methods of genetic analysis which have clarified the heritability of numerous psychiatric disorders to the field of comorbidity. They begin with twin studies and go on to look at research on particular gen...

When I looked at the genetics of placebo effects last June I was struck by the apparent overlap between the genes associated with depression and placebo responses. Does this mean there are biological mechanisms common to antidepressant drug and placebo responses, I wondered, which might partly explain the notorious difficulty demonstrating that antidepressant drugs work better than placebo in clinical trials?

Here I will discuss the genetics of antidepressant drug responses. This is a “bottom up” look at depression biology, which complements other methods like neuroimaging, phenomenological observation and diagnosis, and psychotherapy research. Here I will focus on pharmacodynamics—how the drugs work in the brain—and not address the genetics of drug metabolism by the liver, which also contributes importantly to treatment response. Most of the research has addressed depression, but some of the findings have been extended to treatment of anxiety disorders with antidepressants....

Mark Tonelli, a pulmonologist at the University of Washington who is also trained in philosophy, has written a series of papers which put the role of clinical trial results in perspective and argue for considering several other kinds of information when making clinical decisions. Here I will discuss two of his papers and comment on how his arguments apply to psychiatric practice.

In the first, Tonelli notes that clinical trials provide information about populations of patients but not about how an intervention will affect any individual patient. In addition, clinical trials do not include consider values important to the patient, the profession, or society. He goes on to discuss five “topics” relevant to clinical decision making. Three are sources of medical information: clinical research results, clinical experience, and pathophysiological reasoning; the others are patient values and preferences, and system features.  

Clinical trials study treatment effects in research groups that are...

For some time now I’ve been puzzled about the cerebellum. This pair of mini-hemispheres at the underside of the back of the brain contains over half of the brain’s neurons, though it constitutes only ten percent of the its volume. I knew it had a role in controlling movements, but I was surprised to learn at a recent lecture by Jeremy Schmahmann of the Massachusetts General Hospital that the cerebellum has an important role in the regulation of thoughts, emotions, and social behavior.

The input to the cerebellum is mainly from pontine nuclei which receive their afferents from the cerebral cortex. Its output is via efferent fibers connecting to cerebral cortical regions. In addition, there are bidirectional connections with the vestibular system, the spinal cord, and the brainstem.

Past anatomic research had emphasized the cerebellum’s connections with the motor system, but more recent studies have identified input via pontine nuclei from association areas of the parietal, front...

In the last several years, a new level of analysis has shed light on how the brain functions, as well as on what may be going wrong in psychiatric disorders. Studies of cerebral networks map connections between brain regions and the activity of these circuits, and we now have a Human Connectome Project to bring together information about the brain’s connectivity in a standardized way. The subtitle of a popular 2012 book was “How the Brian’s Wiring Makes Us Who We are.” As others have argued , that is certainly an exaggeration, but looking at differences in the activities of brain circuits is an important advance with potential to generate new treatments based on modifying the activities of brain circuits.

Our understanding of the biological basis of mental illness began with correlations of the psychological and behavior effects of brain injuries, strokes, and tumors with postmortem studies of the patients’ brains. Things had advanced by the time I got to medical school—we had x-rays; p...

Mark Solms, a neuropsychologist in Cape Town, South Africa, has for the last two decades been at the center the movement to enrich both psychoanalysis and neuroscience by bringing their perspectives together. He and his colleagues around the world call this "neuropsychoanalysis." The use findings from neuroimaging, psychopharmacology, findings from animal research, as well as what they call the “clinical-pathological” method, which draws on observations from psychotherapy of brain-damaged patients. In 2002, Solms and his colleague Oliver Turnbull published The Brain and the Inner World: An Introduction to the Neuroscience of Subjective Experience. In it they examine neuroscientific findings from the perspective of Freud’s ideas to generate a neuroscience-based picture of conscious experience. The result is the clearest explication of higher-level brain functions I have found so far.

Solms and Turnbull begin with basic concepts of brain organization, some of...