Since the development of selective serotonin reuptake inhibitors there has been a widening of the definition of depression and a decrease in the placebo-drug difference in controlled studies. In the early 1960s, ~33% of depressed patients improved with placebo and 66% with active compounds and current controlled studies suggest that the situation has certainly not improved. The Sequenced Treatment Alternatives to Relieve Depression Study found that response rates to new compounds after the failure of the first antidepressant are low. The monoamine hypothesis of depression was formulated in the mid 1960s based on the antidepressant efficacy of the monoamine reuptake inhibitors, monoamine oxidase inhibitors and the depressogenic effects of reserpine as a monoamine depleter. However, no monoamine-related finding has been found that is diagnostic for depression. A second major hypothesis regarding depression has been the stress cortisol hypothesis. However, blood cortisol levels are not diagnostic of depression. Every psychiatric clinician is convinced that there are patients for whom antidepressants have made the difference between life and death. However, physicians may generalize unjustifiably based on single dramatic cases to a much larger diagnostic group. Perhaps there are many causes of different types of human sadness, and perhaps only some of these involve mechanisms related to monoamines. Thus, Robert H. Belmaker, MD, suggests that perhaps only some kinds of depression are responsive to monoamine affecting antidepressants.

The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this “subgenual” ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended “visceromotor network” of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.

Along with the development of selective sertonin reuptake inhibitors there has been a tremendous widening of the definition of depression and an impressive decrease in the placebodrug difference in controlled studies. In the early 1960s, about one third of depressed patients improved with placebo and two thirds with active compounds. Current controlled studies suggest that the situation has certainly not improved. The Sequenced Treatment Alternatives to Relieve Depression Study found that response rates to new compounds after the failure of the first antidepressant are low. The monoamine hypothesis of depression was formulated in the mid 1960s based on the antidepressant efficacy of the monoamine reuptake inhibitors, monoamine oxidase inhibitors, and the depressogenic effects of reserpine as a monoamine depleter. However, no monoamine-related finding has been found that is diagnostic for depression. A second major hypothesis regarding depression has been the stress cortisol hypothesis. However, blood cortisol levels are not diagnostic of depression. Psychiatric clinicians are convinced that there are patients for whom antidepressants have made the difference between life and death. However, physicians may generalize unjustifiably based on single dramatic cases to a much larger diagnostic group. Perhaps there are many causes of different types of human sadness, and perhaps only some of these involve mechanisms related to monoamines. Thus, perhaps only some kinds of depression are responsive to monoamine affecting antidepressants.

Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.

We describe the eighth case study of a female diagnosed with anti-N-methyl-d-aspartate receptor encephalitis without an identified tumor who presented with floridly psychotic symptoms following a 2-week prodromal phase with new-onset headaches and presyncopal episodes. While hospitalized, the patient had seizures, autonomic dysfunction, involuntary movements, and a decline in mental status. A subsequent assay was positive for anti-N-methyl-d-aspartate receptor antibodies. In contrast to most reported cases, an initial trial with corticosteroids was therapeutically unsuccessful. Subsequent treatment with intravenous immunoglobulins, however, resulted in a prompt, robust clinical response and enabled the patient to be rapidly discharged from the hospital, with minimal neuropsychiatrie sequelae.

Introduction: Evidence from phenomenological, family, genetic, and treatment studies from Western centers have suggested that tic-related obsessive-compulsive disorder (OCD) could be different from non-tic-related OCD. This study from India investigated the differences in OCD with and without tics, with respect to sociode-mographics, symptom profile, and comorbidity, including obsessive-compulsive spectrum disorders, to examine whether the clinical profile of tic-related OCD is similar to that reported previously.

Methods: Fifty subjects with OCD and tics (chronic motor tics and Tourette syndrome) were compared with 141 OCD subjects without tics.

Results: Subjects having OCD with tics tended to be males, and had an earlier onset of illness. They had more of symmetry/aggressive and religious obsessions, and cleaning, ordering/arranging, hoarding, and repeating compulsions and were associated with trichotillomania and hypochondraisis. Stepwise backward (Wald) regression analysis showed that an early age of onset, male gender, aggressive obsessions, cleaning compulsions, and trichotillomania were significantly associated with tic-related OCD.

Conclusion: The findings of this study from India are broadly similar to those reported previously from the West indicating the universality of differences in tic- and non-tic-related OCD. Our findings also support the existing evidence that tics contribute to the heterogeneity of OCD.