Neuropathology of Suicide

Abstract

Neuropathology is one approach to the effort to elucidate the pathophysiology of suicide. Initial neurochemical studies focusing on the roles of serotonin (5-HT) and noradrenaline (NE) abnormalities in brains of suicide victims have been somewhat inconsistent. More recently developed methodologies, including quantitative receptor autoradiography, immunoblotting, immunohistochemistry, cell morphometry, in situ hybridization, Northern analysis, solution hybridization/RNase protection assay, reverse transcriptase polymerase chain reaction, and genotyping, which have already been applied successfully in studies of other disorders of brain structure or function, are now increasingly being adopted for postmortem studies of suicide. These new strategies are adding convergent evidence for brain 5-HT and NE dysfunction in the etiology of suicide susceptibility, refining the neuroanatomical localization of this dysfunction, and in addition, implicating heretofore unsuspected candidate neurotransmitter systems in the neuropathological substrates of suicide susceptibility. It is argued here that the confluence of the availability of suitable postmortem samples and this augmentation of our armamentarium of techniques promises the attainment of important new insights into the biological underpinnings of suicide from postmortem research. It is to be hoped that this new knowledge might inspire novel pharmacotherapeutic strategies for the prevention of suicide.

Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia

“…There are multiple variants associated with synapsin IIa 1,2,3 , which appear on immunoblots and cannot be resolved without further treatment, and will be referred to as synapsin IIa variants or synapsin IIa(v) (Figure 1). The molecular weight (MW) values observed on immunoblots agree with previously reported MWs for synapsin Ia, IIa (1,2,3) , and IIIa (Table 3), and confirm the specificity of the G304 antibody for synapsin. The synapsin bands (Ia, IIa, and IIIa) were found in both the cytosolic and membrane extracts and analyzed together as total synapsin.…”

“…1 The pathogeneses of these diseases are largely unknown, 2,3 but some studies report the hippocampus to be structurally altered in patients with schizophrenia 4 and bipolar disorder. 5,6 Several etiological theories of schizophrenia implicate neuropathology largely in the mesial temporal lobe, including the dopaminergic, 7 glutamatergic, 8 neurodevelopmental, 9 viral, 10 autoimmunity, 11 synaptic alteration, 12 and membrane 13 hypotheses.…”

Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review

“…Indeed, in a recent study, Weike et al (2000) report that, in schizophrenic patients, neuroleptic treatment can reduce PPI deficits. Finally, this model also has construct validity, as PPI dysfunctions have been associated with DA hyperactivity in the brains of IR rats (particularly in the nucleus accumbens; Jones et al 1992), and of schizophrenic patients (Meltzer and Stahl 1976;Weinberger 1987;Bachus and Kleinman 1996;Egan and Weinberger 1997;Abi-Dargham et al 2000). Furthermore, and as already mentioned above, this model offers the advantage of conforming to the neurodevelopmental theory of schizophrenia, since both in schizophrenics and in IR rats, an alteration of the normal development has permanent consequences for subsequent adult behaviour.…”

“…Although it is not within the scope of this review to discuss the different pharmacological and lesion models for PPI disruption (for review, see Swerdlow et al 2000a), we will present here some examples. Dopaminergic dysfunction in the mesolimbic system has been repeatedly implicated in schizophrenia (Snyder 1976;Seeman et al 1984;Bachus and Kleinman 1996;Knable and Weinberger 1997). In line with this dopaminergic hypothesis, PPI deficits can be obtained by acute pharmacological manipulation of the mesolimbic system (Swerdlow et al 1992b).…”

Alterations of hippocampal secreted N-CAM in bipolar disorder and synaptophysin in schizophrenia

“…1 The pathogeneses of these diseases are largely unknown (for review 2,3 ), but some studies report the hippocampus to be structurally altered in patients with schizophrenia 4 and bipolar disorder. 5,6 A number of neurobiological theories have been proposed to explain the etiology of schizophrenia.…”