Mark Solms

The molecular genetics of cognition: dopamine, COMT and BDNF

The important contribution of genetic factors to the development of cognition and intelligence is widely acknowledged, but identification of these genes has proven to be difficult. Given a variety of evidence implicating the prefrontal cortex and its dopaminergic circuits in cognition, most of the research conducted to date has focused on genes regulating dopaminergic function. Here we review the genetic association studies carried out on catechol‐O‐methyltransferase (COMT) and the dopamine receptor genes, D1, D2 and D4. In addition, the evidence implicating another promising candidate gene, brain‐derived neurotrophic factor (BDNF) in neuropsychological function, is assessed. Both the COMT val158met polymorphism and the BDNF val66met variant appear to influence cognitive function, but the specific neurocognitive processes involved continue to be a matter of debate. Part of the difficulty is distinguishing between false positives, pleiotropy and the influence of a general intelligence factor, g. Also at issue is the complexity of the relevant neuromolecular pathways, which make the inference of simple causal relationships difficult. The implications of molecular genetic cognitive research for psychiatry are discussed in light of these data.

The neuropsychology of dreams : a clinico-anatomical study

Contents: Foreword. Preface. Introduction. The Classical Case Reports of Charcot-Wilbrand Syndrome. Charcots Variant of the Charcot-Wilbrand Syndrome: Cessation or Restriction of Visual Dream-Imagery. Wilbrands Variant of the Charcot-Wilbrand Syndrome: Global Cessation of Reduction of Dreaming. The Neglected Psychosurgical Literature. The Problem of REM Sleep. Other Abnormalities of Dreaming Described in the Literature. Summary of Provisional Conclusions and Hypotheses. Description of the Present Research. The Charcot-Wilbrand Syndrome Reconsidered. Two Patients With Nonvisual Dreaming. Anatomical Correlates of Nonvisual Dreaming. Clinical Correlates of Nonvisual Dreaming. Some Incidental Observations on Modal Specificity. Initial Theoretical Remarks. Anatomical Correlates of Global Cessation of Dreaming. Are Dreams Generated by Brainstem Mechanisms? Clinical Correlates of Global Cessation of Dreaming. Further Theoretical Remarks. Ten Patients With Varying Degrees of Confusion Between Dreams and Reality. Clinico-Anatomical Correlates of the Confusion Between Dreams and Reality. Nine Patients With Recurring Nightmares. Clinico-Anatomical Correlates of Recurring Nightmares. Miscellaneous Observations (Including Normal Dreaming). Summary of Results and Nosological Conclusions. Final Theoretical Remarks: A Model of the Normal Dream Process. Appendix: Glossary of Nosological Terms.

What is consciousness

In the past few years scientists and scholars in a variety of disciplines have been making concerted efforts to answer an ancient question, namely, How exactly do the physical processes in the brain cause consciousness? What is distinctive about the way in which modern scientists and scholars are approaching this question is that they are treating it as a scientific problem rather than a metaphysical one. This transition reflects the air of expectation in contemporary cognitive science to the effect that an empirical solution is imminent to a philosophical problem that previously was considered insoluble. Nevertheless, a recent authoritative review of the publications of such leading contemporary workers in the field as Francis Crick, Daniel Dennett, Gerald Edelman, Roger Penrose, and Israel Rosenfield has concluded that they have all failed to provide a satisfactory answer to the question (Searle 1995a). The present paper makes a psychoanalytic contribution to this interdisciplinary effort and provides an alternative answer to the question, based on Freuds conceptualization of the problem of consciousness. The paper takes a concrete example from Searles review, reanalyses it within Freuds metapsychological frame of reference, and shows how this frame provides a radical solution to the problem. This implication of Freuds work has not hitherto been recognized and so has not received the attention it deserves.

The neural substrates of mindfulness: An fMRI investigation

“Mindfulness” is a capacity for heightened present-moment awareness that we all possess to a greater or lesser extent. Enhancing this capacity through training has been shown to alleviate stress and promote physical and mental well-being. As a consequence, interest in mindfulness is growing and so is the need to better understand it. This study employed functional magnetic resonance imaging (fMRI) to identify the brain regions involved in state mindfulness and to shed light on its mechanisms of action. Significant signal decreases were observed during mindfulness meditation in midline cortical structures associated with interoception, including bilateral anterior insula, left ventral anterior cingulate cortex, right medial prefrontal cortex, and bilateral precuneus. Significant signal increase was noted in the right posterior cingulate cortex. These findings lend support to the theory that mindfulness achieves its positive outcomes through a process of disidentification.

Neuropsychological task performance in bipolar spectrum illness: genetics, alcohol abuse, medication and childhood trauma

INTRODUCTION Impaired executive and memory function is a putative genetic trait marker of bipolar I disorder (BPD I). Although executive/memory function has been posited to be an endophenotype of BPD I, it is unclear whether this extends to bipolar spectrum illness. It is also unclear to what extent non-genetic factors such as childhood abuse, alcoholism and medication influence neurocognitive function. We assessed the neuropsychological performance of a large cohort of bipolar disorder probands and their affectively ill and healthy family members, while controlling for self-reported childhood sexual and emotional abuse, emotional neglect, alcohol abuse and medication. METHODS A total of 230 largely euthymic participants from 47 families, comprising 49 subjects with BPD I, 19 with bipolar II disorder (BPD II), 44 with recurrent major depression (MDE-R), 33 with a single lifetime episode of depression (MDE-S), 20 with other DSM-IV diagnoses and 65 unaffected relatives, were assessed with a battery of neuropsychological tasks. RESULTS Sexual abuse, emotional abuse and emotional neglect scores were associated with poorer cognitive performance. After controlling for childhood trauma, the BPD I group performed worse than unaffected relatives on tests of visual recall memory as well as verbal recall and recognition memory. In contrast, individuals with BPD II and bipolar spectrum illness did not differ significantly from unaffected relatives. Treatment with lithium and antipsychotic medication was associated with reduced executive and verbal recognition memory function. After controlling for medication and other covariates, only verbal recall memory was significantly impaired in the BPD I cohort. CONCLUSIONS Verbal recall deficits may be one manifestation of a genetically driven dysfunction of frontal-striatal cortical networks in BPD I.

The Conscious Id

Two aspects of the body are represented in the brain, and they are represented differently. The most important difference is that the brain regions for the two aspects of the body are associated with different aspects of consciousness. Very broadly speaking, the brainstem mechanisms derived from the autonomic body are associated with affective consciousness, and the cortical mechanisms derived from the sensorimotor body are associated with cognitive consciousness. Moreover, the upper brainstem is intrinsically conscious whereas the cortex is not; it derives its consciousness from the brainstem. These facts have substantial implications for psychoanalytic metapsychology because the upper brainstem (and associated limbic structures) performs the functions that Freud attributed to the id, while the cortex (and associated forebrain structures) performs the functions he attributed to the ego. This means that the id is the fount of consciousness and the ego is unconscious in itself. The basis for these conclusions, and some of their implications, are discussed here in a preliminary fashion.

Confabulation: Motivated reality monitoring

The study addressed the hypothesis that the content of confabulation is emotionally biased. Confabulating amnesic patients were compared with amnesic non-confabulating patients in a memory recognition experiment that manipulated the valence (pleasant, unpleasant), temporal source (past, present, future) and selection agent (self, other) of the to-be-recognised memories. The results revealed that confabulating patients were more likely than amnesic non-confabulating patients to incorrectly recognise past autobiographical events or thoughts as currently relevant memories, and this was more pronounced for pleasant compared to unpleasant events. These findings suggest that motivational factors, along with defective reality and temporality monitoring, contribute to confabulation.

Genotype and childhood sexual trauma moderate neurocognitive performance: a possible role for brain-derived neurotrophic factor and apolipoprotein E variants

BACKGROUND Limited success in the identification of genetic variants underpinning psychiatric illness has prompted attempts to elucidate gene-environment interactions and illness-associated endophenotypes. Here we measured childhood sexual abuse, a potential environmental risk factor, and verbal and visual recall and recognition memory, a possible illness-associated endophenotype in a cohort of bipolar disorder (BPD) subjects and their relatives. We predicted that memory would be affected by sexual trauma and that a number of functional polymorphisms previously implicated in BPD and cognition would moderate the effect of psychological trauma on memory. METHODS A cohort of 350 individuals from 47 BPD families was recruited, tested with a neuropsychological battery, and given the Childhood Trauma Questionnaire (CTQ). Eleven different genetic variants previously found to be relevant to BPD or memory dysfunction were typed. RESULTS As predicted, scores on the sexual abuse scale of the CTQ were negatively associated with memory performance. Furthermore, the low-activity Met allele of the brain-derived neurotrophic factor (BDNF) gene and the epsilon4 allele of the apolipoprotein E gene interacted with sexual abuse scores to result in reduced memory test performance. CONCLUSIONS Apolipoprotein E and BDNF exert a neurotrophic effect in response to cellular injury. Their possible moderation of the association between sexual abuse and memory performance might indicate that there is some degree of overlap in the pathophysiological mechanisms by which psychological and physical trauma impact brain function. The finding of an environmental effect on memory performance and a gene-environment interaction on this hypothetical endophenotype of BPD illustrates the difficulty of identifying genetically and phenotypically simple intermediate traits for molecular genetic studies.

Neurocognitive function as an endophenotype for genetic studies of bipolar affective disorder

The genetic basis of bipolar affective disorder remains opaque despite years of intensive investigation. One of the most serious difficulties for genetic research is the enormous phenotypic heterogeneity of psychiatric illnesses. As a response to this problem, geneticists have searched for alternative strategies to identify those individuals at genetic risk for developing the disorder. One approach is to use endophenotypes or intermediate traits. Gottesman and Gould (2003), in their discussion of endophenotypes, suggest five criteria that should be characteristic of a trait in order for it to qualify as an endophenotype. These five criteria are used in order to assess the viability of using measures of neuropsychological dysfunction as endophenotypes for genetic studies of bipolar disorder. A review of the literature suggests that executive dysfunction is characteristic of people with bipolar disorder in both the acute and chronic stages of the illness, that neurocognitive function is influenced by genetic factors and that neuropsychological deficits have been reported in the nonaffected relatives of bipolar probands. Nevertheless, it is unclear whether neuropsychological dysfunction co-segregates with affectively ill individuals. We conclude that the use of neurocognitive markers of bipolar illness suffers from a number of serious drawbacks but given the absence of more appropriate endophenotypes, the neuropsychological profiling of probands and their relatives may nevertheless prove to be a worthwhile exercise.

Inverted Vision After Frontal Lobe Disease

A case of bifrontal abscesses is reported. The patient claimed that he sometimes saw the world as if it were upside-down. A review of the literature reveals that, since 1805, 21 similar cases have been documented. The present case is unusual in that the neuropsychological status of the patient is investigated in some detail, and in that it seems to be the first report of inverted vision in a case of frontal lobe disease.