Neural systems underlying affective disorders

Three main approaches are used to explore the neural correlates of mood disorder: neuropsychological studies, neuroimaging studies and post-mortem investigations. Lesion studies implicate disturbances in the frontal lobe, basal ganglia, striatum and anterior temporal cortex. Early neurocognitive and neuropathological investigations led to a ‘hypofrontality’ hypothesis of unipolar and bipolar depression, but functional neuroimaging has revealed a more complex picture. Thus, increased metabolism may occur in the subgenual anterior cingulate gyrus in resting-state studies of depression and sad-mood induction. Antidepressants may reduce this activity. Amygdala hyperactivation also is associated with affective disorders. Task-related studies reveal abnormal biases in memory, the experience of pleasure and the perception of emotional facial expressions. There is still little clarity whether the abnormalities in brain activation represent state or trait characteristics of affective disorders. famously suffered from accidental damage of the frontal lobe in 1848. The iron bar that forced its way through his cranium caused lesions in the left and right ventromedial regions of the prefrontal cortex (as reconstructed by Damasio et al, 1994). Mr Gage, who was an exemplary citizen before the accident, afterwards became a completely different person – impatient, rude and prone to outbursts of anger and rage. Blumer & Benson (1975) proposed that personality changes after frontal lobe damage could be classified under ‘pseudopsychopathy’ or ‘pseudodepression’. Pseudodepression was more frequently associated with lesions of the left frontal lobe and was characterised by apathy, loss of initiative, low mood and reduced sexual interest. Several lesion studies have demonstrated that damage to left frontal areas contributed specifically to depressive syndromes, whereas the consequences of right prefrontal lobe damage are less clear and may be associated with pseudopsychopathic behaviour or mania. Although the lateralisation effect has not been found in all studies, the association of mood disturbance with prefrontal lesions is widely recognised. Studies that reviewed the structural brain scans of stroke patients found an association between subsequent mood changes and infarctions of the Simon Surguladze is a research worker in the Section of Neuroscience and Emotion, King’s College London, based at the Institute of Psychiatry (De Crespigny Park, Denmark Hill, London SE5 8AF, UK). Paul Keedwell is an honorary clinical research worker and specialist registrar at the Mood Disorder Clinic of the Maudsley Hospital, London. Mary Phillips is Head of the Section of Neuroscience and Emotion and professor and honorary consultant psychiatrist in the Division of Psychological Medicine, Institute of Psychiatry and GKT School of Medicine. The Section’s research programme includes studies of neurobiological mechanisms underlying mood dysregulation in patients with affective disorders, schizophrenia, depersonalisation and obsessive–compulsive disorder. Neural systems underlying affective disorders 447 Advances in Psychiatric Treatment (2003), vol. 9. http://apt.rcpsych.org/ frontal lobe and basal ganglia, particularly the head of the caudate. Similar studies of trauma cases and tumour patients have suggested that dorsolateral rather than ventral frontal lobe lesions are important for depressive mood change, but these are heterogeneous conditions and there are inconsistent findings. The importance of temporal lobe pathology in the genesis of organic depression is suggested by several studies demonstrating a link between depression and lateralised temporal lobe epilepsy, the presence of temporal lobe plaques in multiple sclerosis and the extent of temporal involvement in Alzheimer ’s disease sufferers. Pathology in the corpus striatum, an area believed to be important for regulating the pleasure response (among other functions), is also implicated in these studies. The nigrostriatal pathway is affected in Parkinson’s disease, a condition known to have a high association with depression. There are indications from post-mortem studies that selective cell loss in the ventral tegmentum (an essential component of the dopamine-mediated ‘reward system’ – see below) must also occur for prominent mood symptoms to be present. The findings from lesion studies are consistent with disruption in two known anatomical pathways, as illustrated by Mayberg (2000): the orbital–frontal–striatal–thalamic circuit and the basotemporal–limbic circuit, which links the frontal cortex to the anterior temporal cortex.