Localized decrease in serotonin transporter-immunoreactive axons in the prefrontal cortex of depressed subjects committing suicide.

A variety of postmortem brain studies and clinical investigations have provided evidence that reduced serotonin neurotransmission is associated with suicidal behavior and depression, and several serotonergic parameters have been found to be altered in the prefrontal cortex of suicide victims. However, the integrity of the serotonin innervation of the prefrontal cortex in mood disorders has not been directly investigated. The present study used immunocytochemical methods and an antibody against the serotonin transporter to examine the relative density of serotonin axons in the dorsolateral prefrontal cortex of suicide victims with a diagnosis of major depression. The mean total length of serotonin transporter-immunoreactive axons per unit area was unchanged in layers 2 and 4 of area 46 in the depressed suicide subjects compared to controls, but was significantly (P < 0.01) decreased by 24% in layer 6 in the depressed suicide group. The total length of serotonin transporter-positive axons in layer 6 was reduced in eight of the 12 depressed suicide subjects compared to their matched control subjects. These findings reveal that depressed subjects who have committed suicide exhibit a lamina-specific reduction in a marker of serotonin axons in the dorsolateral prefrontal cortex that may reflect an alteration in cortical serotonin neurotransmission.

Interferon-alpha2a/ribaviran versus interferon-alpha2a alone for the retreatment of hepatitis C patients who relapse after a standard course of interferon.

AIM: To compare the efficacy of a descalating dose of interferon (48 weeks) versus a combination therapy of interferon and ribavirin (24 weeks) in hepatitis C positive subjects who relapsed within six months of cessation of a standard six month course of interferon three million units thrice weekly. METHODS: All 32 subjects had biopsy proven chronic hepatitis C, were PCR positive and had elevated transaminase enzymes at least one and a half times the upper limit of normal. Subjects were randomly assigned to either a descalating dose of interferon-alpha-2a; six million units thrice weekly for 24 weeks followed by 3 MIU 3x for 24 weeks or interferon three million units thrice weekly for 24 weeks plus ribavirin 1,000 mg/day for 12 weeks. A complete virological response was defined as a negative PCR for HCV RNA at 24 weeks after cessation of therapy. RESULTS: Sixteen patients were assigned to each arm and the sustained virological response was 50% for both the interferon and combination therapy arm (pNS). The biochemical response correlated with the virological response; 7/8 virological responders in the interferon alone had normalisation of transaminase 24 weeks post treatment as did 8/8 of those in the combination arm. One patient withdrew from treatment in the descalating interferon group and three required dose reduction. No subjects in the combination arm discontinued therapy but dose reduction was required in three subjects. CONCLUSION: High dose descalating interferon-alpha 2a and a combination of interferon-alpha 2a and ribavirin were effective in achieving a sustained virological response in 50% of subjects who had relapsed after a standard six month course of interferon.

Decreased density of tyrosine hydroxylase-immunoreactive axons in the entorhinal cortex of schizophrenic subjects.

BACKGROUND: We recently reported a laminar-specific reduction in the density of tyrosine hydroxylase (TH)-immunoreactive axons in the prefrontal cortex of subjects with schizophrenia. In this report, we extend these investigations to the entorhinal cortex (ERC), another candidate site of dysfunction in this disorder. METHODS: Using immunocytochemical techniques and blind quantitative analyses, we determined the density of TH-immunoreactive axons in the rostral subdivision of the ERC from seven matched pairs of schizophrenic and control subjects. RESULTS: The relative density of TH-labeled axons was significantly decreased by over 60% in layers 3 and 6, but not in layer 1, of the ERC in schizophrenic subjects. In contrast, in the prefrontal cortex of the same subjects, labeled axon density was significantly decreased by 62% only in layer 6. Furthermore, the length of TH-labeled axons did not differ between six matched pairs of nonschizophrenic psychiatric and control subjects in any layer of the ERC. Finally, the density of TH-labeled axons in the ERC of cynomolgus monkeys chronically treated with haloperidol was not reduced relative to control animals. CONCLUSIONS: These findings reveal regional- and laminar-specific alterations in TH-immunoreactive axons that appear to be specific to the pathophysiology of schizophrenia.

Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects.

OBJECTIVE: Abnormalities in dopamine neurotransmission in the prefrontal cortex have been implicated in the pathophysiology of schizophrenia. However, the integrity of the dopamine projections to the prefrontal cortex in this disorder has not been directly examined. METHOD: The authors employed immunocytochemical methods and antibodies against tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis, and the dopamine membrane transporter to examine dopamine axons in the dorsomedial prefrontal cortex (area 9) from 16 pairs of schizophrenic and matched control subjects. RESULTS: Compared to the control subjects, the total length of tyrosine hydroxylase-immunoreactive axons was unchanged in the superficial and middle layers of the schizophrenic subjects but was reduced by an average of 33.6% in layer 6. The total length of tyrosine hydroxylase-positive axons in layer 6 was decreased in 13 of the schizophrenic subjects compared to their control subjects. Axons immunoreactive for the dopamine membrane transporter showed a similar pattern of change. In contrast, axons labeled for the serotonin transporter did not differ between schizophrenic and control subjects in any layer examined. In addition, the density of tyrosine hydroxylase-containing axons did not differ between monkeys chronically treated with haloperidol and matched control animals. CONCLUSIONS: These findings reveal that schizophrenia is associated with an altered dopamine innervation of prefrontal cortex area 9 that is lamina- and neurotransmitter-specific and that does not appear to be a consequence of pharmacological treatment. Together, these data provide direct evidence for a disturbance in dopamine neurotransmission in the prefrontal cortex of schizophrenic subjects.

A new method for toilet training developmentally disabled children.

20 profoundly retarded children (4 to 12 yr.) were trained, using a variety of relaxation and tension activities designed to help them differentiate and gain control of the toileting musculature. Operant techniques were used to reinforce appropriate urination. The post-training scores of the experimental and control groups differed significantly for both accidental and appropriate urination.